The effects of Terminalia catappa leaf extracts (TCE) have been widely investigated, including its antioxidative, anti‐inflammatory, and antidiabetic activity, as well as its antimetastatic effects ...on several types of human cancer. However, no study has examined the antimetastatic potential of TCE in cervical cancer cells. This study aimed to elucidate the potential antimetastatic properties of ethanol extracts of Terminalia catappa in 12‐O‐tetradecanoylphorbol‐13‐acetate treated human cervical cancer cells and investigate the signaling pathway of this process. We demonstrated that TCE elicited very low cytotoxicity and significantly inhibited cellular migration and invasion in human HeLa and SiHa cervical cancer cells. Moreover, the gelatin zymography, reverse transcription‐polymerase chain reaction (RT‐PCR), and real‐time PCR analysis revealed that the activity and mRNA level of matrix metalloproteinase‐9 (MMP‐9) were inhibited by TCE in a concentration‐dependent manner. The Western blot results demonstrated that the highest concentration of TCE (100 μg/ml) reduced the phosphorylation of extracellular signal‐regulated kinases 1/2 (ERK1/2) by 46% in the HeLa cell lines. In conclusion, it was revealed that TCE exerted antimetastatic effects on cervical cancer cells by inhibiting the expression of MMP‐9 through the ERK1/2 pathway.
Oral squamous cell carcinoma (OSCC) is a prevalent and lethal malignancy with a diverse etiology. LINC00312 is a long intergenic non-coding RNA that functions as a signal hub to regulate the ...progression and treatment of head and neck cancer. The aim of this study was to evaluate the effect of
single nucleotide polymorphisms (SNPs) on the development of oral cancer. Two
SNPs, namely rs12497104 and rs164966, were investigated among 469 male patients with cancer of buccal mucosa and 1194 gender- and age-matched controls. No significant correlation was observed between these two SNPs and the occurrence of OSCC in the case and control groups. While assessing the clinicopathological features, carriers of at least one minor allele of rs164966 (GA and GG) were less prone to develop lymph node metastasis (adjusted odds ratio AOR, 0.666; 95% confidence interval CI, 0.447-0.991;
=0.045) in comparison with homozygous carriers of the major allele (AA). Subsequent stratifying surveys revealed that this genetic association with nodal spread was seen only in cases who habitually chewed betel quid (AOR, 0.616; 95% CI, 0.386-0.985;
=0.042) or smoked cigarettes (AOR, 0.612; 95% CI, 0.393-0.953;
=0.029), but undetected in cases free of these main behavioral risks. Our results indicate an interactivity of
rs164966 with lifestyle-related risks on modulating OSCC progression.
Oral cancer, which is the fourth most common cancer in Taiwanese men, is associated with environmental carcinogens. The possibility that genetic predisposition in nuclear factor-kappa B ...(NF-κB)-signaling pathways activation is linked to the development of oral squamous cell carcinoma (OSCC) requires investigation. The current study examines associations between polymorphisms within promoter regions of NFKB1 encoding NF-κB1 and NFKBIA encoding IkappaBalpha (IκBα) with both the susceptibility to develop OSCC and the clinicopathological characteristics of the tumors.
Genetic polymorphisms of NFKB1 and NFKBIA were analyzed by a real-time polymerase chain reaction (real-time PCR) for 462 patients with oral cancer and 520 non-cancer controls. We found that NFKB1 -94 ATGG1/ATGG2, -94 ATGG2/ATGG2, and the combination of -94 ATGG1/ATGG2 and ATGG2/ATGG2 genotypes NFKBIA -826 T (CT+TT) and -881 G (AG+GG) allelic carriages, were more prevalent in OSCC patients than in non-cancer participants. Moreover, we found that NFKB1 or NFKBIA gene polymorphisms seem to be related to susceptibility to develop oral cancer linked to betel nut and tobacco consumption. Finally, patients with oral cancer who had at least one -519 T allele of the NFKBIA gene were at higher risk for developing distant metastasis (P<.05), compared with those patients CC homozygotes.
Our results suggest that NFKB1 -94 ATTG2, NFKBIA -826 T, and -881 G alleles are associated with oral carcinogenesis. The combination of NFKB1 or NFKBIA gene polymorphisms and environmental carcinogens appears related to an increased risk of oral cancer. More importantly, the genetic polymorphism of NFKBIA -519 might be a predictive factor for the distal metastasis of OSCC in Taiwanese.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Magnolol is a natural compound extracted from Chinese herbal medicine and can induce apoptosis in numerous types of cancer cells. However, the molecular mechanisms of magnolol in oral cancer are ...still unclear. In this study, we investigated the anti-cancer effects and underlying mechanisms of magnolol in human oral cancer cell lines. Our results exhibited that magnolol inhibited the cell proliferation via inducing the sub-G1 phase and cell apoptosis of HSC-3 and SCC-9 cells. The human apoptosis array and Western blot assay showed that magnolol increased the expression of cleaved caspase-3 proteins and heme oxygenase-1 (HO-1). Moreover, we proved that magnolol induces apoptosis in oral cancer cell lines via the c-Jun N-terminal kinase (JNK)1/2 and p38 pathways. Overall, the current study supports the role for magnolol as a therapeutic approach for oral cancer through JNK1/2- and p38-mediated caspase activation.
Objectives
Oral cancer is the most common head and neck malignancy, and it is associated with a high recurrence rate and lymph node metastasis potential. YKL-40, also known as chitinase-3-like ...protein 1 (CHI3L1), is a secreted glycoprotein that serves as a biomarker in several diseases. It also plays a crucial role in regulating many characteristics of cancer, such as cell growth, migration, anti-apoptosis, and angiogenesis. Accumulating evidence supports the link between single-nucleotide polymorphisms (SNPs) and oral cancer, but no report on the association between
CHI3L1
polymorphisms and oral cancer is available. Thus, the present study evaluated the contribution of
CHI3L1
SNPs to oral cancer susceptibility and clinicopathology.
Materials and methods
This study recruited a total of 2362 subjects, comprising 1190 healthy male controls and 1172 male patients with oral cancer. Allelic discrimination of the
CHI3L1
polymorphisms − 1371 G>A (rs6691378), − 247 G>A (rs10399805), − 131 C>G (rs4950928), and + 2950 T>C (rs880633) was assessed through real-time polymerase chain reaction.
Results
We detected a significant association of rs10399805 and rs6691378 with the risk of oral cancer (AOR, 1.537; 95% CI, 1.089–2.168;
p
= 0.014; AOR, 1.561; 95% CI, 1.131–2.156;
p
= 0.007, respectively) after adjustment for three potential confounders, smoking, betel nut chewing, and alcohol consumption. Moreover, we found that oral cancer patients carrying the homozygous A/A genotype of the rs10399805 (
p
= 0.035) or rs6691378 polymorphism (
p
= 0.023) showed a significantly lower risk of lymph node metastasis. Moreover, according to the Genotype-Tissue Expression database, the rs10399805 and rs6691378 polymorphisms in the promoter region were associated with decreased levels of CHI3L1 mRNA.
Conclusions
In conclusion, we found that the homozygous mutant allele of rs10399805 and rs6691378 appeared to have significantly lower risk of lymph node metastasis and associated with its mRNA levels in oral cancer.
Clinical relevance
The CHI3L1 polymorphisms rs10399805 and rs6691378 may act as biomarkers for predicting lymph node metastasis in oral cancer patients.
Epithelial-mesenchymal transition (EMT) is strongly correlated with tumor metastasis and contains several protein markers, such as E-cadherin. Carbonic anhydrase III (CA III) exhibits low carbon ...dioxide hydratase activity in cancer. However, the detailed mechanisms of CA III and their roles in oral cancer are still unknown. This study established a CA III-overexpressed stable clone and observed the expression of CA III protein in human SCC-9 and SAS oral cancer cell lines. The migration and invasion abilities were determined using a Boyden chamber assay. Our results showed that the overexpression of CA III protein significantly increased the migration and invasion abilities in oral cancer cells. Moreover, a whole genome array analysis revealed that CA III regulated epithelial-mesenchymal transition by reducing the expression of epithelial markers. Data from the GEO database also demonstrated that CA III mRNA is negatively correlated with CDH1 mRNA. Mechanistically, CA III increased the cell motility of oral cancer cells through the FAK/Src signaling pathway. In conclusion, this suggests that CA III promotes EMT and cell migration and is potentially related to the FAK/Src signaling pathway in oral cancer.
Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), with high affinity to a myriad of RNA transcripts, has been shown to elicit promotive effects on tumorigenesis and metastasis. Yet, the ...functional involvement of IGF2BP2 in the progression of oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, we showed that IGF2BP2 was upregulated in head and neck cancer, and high levels of IGF2BP2 were associated with poor survival. In
experiments, IGF2BP2 promoted migration and invasion responses of OSCC cells. Moreover, we identified an IGF2BP2-regulated gene, EREG, which functioned as a modulator of OSCC invasion downstream of IGF2BP2. In addition, EREG expression triggered the epithelia-mesenchymal transition (EMT) in OSCC, as evidenced by the observation that knockdown of EREG weakened the induction of EMT mediated by IFG2BP2, and replenishment of EREG favored the EMT in IGF2BP2-depleted cells. Such IGF2BP2-regulated EREG expression, EMT, and cell invasion were dependent on the activation of FAK/Src signaling pathway. Collectively, these findings suggest that EREG, serving as a functional mediator of IGF2BP2-regulated EMT and cell invasion in oral cancer, may be implicated as a potential target for antimetastatic therapies.
Oral squamous cell carcinoma (OSCC), an epithelial malignancy affecting a variety of subsites in the oral cavity, is prevalent in Asia. The survival rate of OSCC patients has not improved over the ...past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. Improvement in therapeutic strategies and tailored treatment options is an unmet need. To unveil the mutational spectrum, whole-exome sequencing of 120 OSCC from male individuals in Taiwan was conducted. Analyzing the contributions of the five mutational signatures extracted from the dataset of somatic variations identified four groups of tumors that were significantly associated with demographic and clinical features. In addition, known (
,
,
,
,
,
,
,
, and
) and novel (
and
) genes that were significantly and frequently mutated in OSCC were discovered. Further analyses of gene alteration status with clinical parameters revealed that the tumors of the tongue were enriched with copy-number alterations in several gene clusters containing
and
. Through defining the catalog of targetable genomic alterations, 58% of the tumors were found to carry at least one aberrant event potentially targeted by US Food and Drug Administration (FDA)-approved agents. Strikingly, if targeting the p53-cell cycle pathway (
and
) by the drugs studied in phase I-III clinical trials, those possibly actionable tumors are predominantly located in the tongue, suggesting a better prediction of sensitivity to current targeted therapies. Our work revealed molecular OSCC subgroups that reflect etiological and prognostic correlation as well as defined the landscape of major altered events in the coding regions of OSCC genomes. These findings provide clues for the design of clinical trials for targeted therapies and stratification of OSCC patients with differential therapeutic efficacy.
In this article, we present a new method to control the direction of traveling waves in either an x-direction or y-direction on a two-dimensional square plate. The core structure was composed of a ...piezoelectric serial bimorph with four electrodes. Each electrode was spatially designed to activate one of the bending modes and which included the ability to reduce adjacent modes and minimize interference. Our new method differs from other reported methods in that the four electrodes were driven at designated resonant frequencies. In our wave generator, different driving amplitudes and phases were applied to induce the traveling waves to propagate in a specific direction. To design the directional movement and to better understand the pattern of induced traveling waves, an analytical solution was derived to assist in the design of the four driving electrodes. Using our newly developed analytical method, traveling waves can be controlled to travel in either the x-direction or y-direction using two different sets of electrodes, where each electrode can be driven at a specific but different bending mode. We found that both the voltage ratio and phase difference between the two driving electrodes are important factors for optimization.
Oral cancer, the fourth most common cancer among men in Taiwan, is associated with environmental carcinogens. Tissue inhibitor of metalloproteinase-3 (TIMP3), a member of the TIMP family, is the only ...protein that binds to the extracellular matrix for suppressing cancer cell growth, angiogenesis, migration, and invasion. The association of TIMP3 polymorphism with oral cancer susceptibility, however, has not yet been reported. In this study, 1947 participants-1200 healthy male controls and 747 male patients with oral cancer-were recruited. Allelic discrimination of TIMP3 -1296 T > C (rs9619311), TIMP3 C > T (rs9862), and TIMP3 C > T (rs11547635) polymorphisms were assessed through real-time polymerase chain reaction. The authors discovered that individuals carrying the polymorphic rs9862 allele are more susceptible to oral cancer odds ratio (OR), 1.5; 95% confidence interval (CI), 1.2-1.9; adjusted OR (AOR), 1.6; 95% CI, 1.2-2.1 after adjustment for betel quid chewing, alcohol, and tobacco consumption. Among 601 betel quid chewers, the TIMP3 polymorphism rs9862 T/T carriers had a 32.2-fold (95% CI, 20.2-51.3) increased oral cancer risk compared with those carrying C/C and not chewing betel quid. In addition, the authors observed a significant association between rs9862 variants and large tumors (OR, 1.5; 95% CI, 1.0-2.3) development. Moreover, TIMP3 plasma levels significantly increased in oral cancer patients who have large tumor or carry T allele rs9862 polymorphism. In conclusion, these results suggest that gene-environment interactions between the TIMP3 rs9862 polymorphisms and betel quid may alter oral cancer susceptibility and tumor growth in Taiwanese men.
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