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157 Clinicopathological implications of cyclin B1, cdc2, p16 and p53 expression in breast cancer
... [4] However, conflicting results have been reported in different studies. [9][10][11][12][13][14][15][16][17][18][19] A meta-analysis conducted in 2017 found significant associations between high expression of cyclin B1 and B2 proteins and worse prognosis and several clinicopathological parameters. [4] Since then, contradictory reports have emerged. ...
... The full-text review was conducted for 75 articles, then 58 studies were removed (45 contained irrelevant data, 9 were cell line or animal experimental studies, 3 articles used overlapping populations, and 1 was a review article.) A total of 17 studies (11 studies from the search, [20][21][22][23][24][25][26][27][28][29][30] and 6 studies which were included in the previous meta-analysis [10,12,13,15,18,19] ) were used for this meta-analysis. ...
... The individual studies on the prognostic significance of cyclin B1 and CCNB1 showed an association between worse prognosis and their expression with varying statistical significance. [10,12,13,15,19,[21][22][23][25][26][27][28][29] The significant prognostic impact of cyclin B1 expression is consistent with previous findings. [4] Interestingly, the OS and DSS showed statistically significant results with no heterogeneity, while the DFS showed significant considerable heterogeneity. ...
Background
Cyclin B1 and cyclin B2 are key regulators of cell cycle progression and have been implicated in the prognostic significance of various cancers. This meta-analysis aimed to evaluate the prognostic value of cyclin B1 and B2 expression in breast cancer.
Methods
A comprehensive literature search was conducted on Pubmed, Embase, MEDLINE, Web of Science, and Cochrane library. Studies with survival data and clinicopathological parameters associated with cyclin B1 and B2 or CCNB1 and CCNB2 genes were included. Survival data and clinicopathological parameters associated with cyclin B1 and B2 expression were extracted. Pooled hazard ratios and odds ratios with 95% confidence intervals were calculated. Subgroup analysis was conducted to assess heterogeneity. Publication bias was evaluated.
Results
A total of 23 studies were included in the analysis. High expression of cyclin B1 was significantly associated with worse overall survival (hazard ratio [HR] = 1.69, P < .01), disease-specific survival (HR = 1.71, P < .01), and disease-free survival (HR = 2.01, P = .01). High expression of cyclin B2 was associated with worse disease-specific survival (HR = 2.46, P = .02). Clinicopathological parameters did not show significant associations with cyclin B1 and B2 expressions. When data on cyclin B1 and B2 were combined, a significant age-related difference was found (odds ratio = 0.62, P = .04).
Conclusions
This meta-analysis provides evidence supporting the prognostic significance of cyclin B1 and B2 expression in breast cancer. High expression of cyclin B1 and B2 is associated with worse survival, indicating their potential as prognostic markers in breast cancer.
... Of the remaining 18 candidate articles, 3 publications provide cyclin B expression only and 5 publications, analyzing the relationship between cyclin B expression and clinicopathological/prognostic significance, could not be extracted with sufficient information. Ten eligible publications [21][22][23][24][25][26][27][28][29][30] were therefore included in the meta-analysis. ...
... Immunohistochemistry was utilized to assess cyclin B expression in all studies. Of the 10 studies included in this meta-analysis, 6 studies [21,24,25,[27][28][29] investigated the association between cyclin B expression and prognostic significance, 2 studies [23,30] [22,26] studied both. In these 10 studies, 3 publications [24,28,29] investigated the total cyclin B expression while 1 publication [22] studied the cyclin B2 expression and 6 publications [21,23,[25][26][27]30] studied the cyclin B1 expression. ...
... Of the 10 studies included in this meta-analysis, 6 studies [21,24,25,[27][28][29] investigated the association between cyclin B expression and prognostic significance, 2 studies [23,30] [22,26] studied both. In these 10 studies, 3 publications [24,28,29] investigated the total cyclin B expression while 1 publication [22] studied the cyclin B2 expression and 6 publications [21,23,[25][26][27]30] studied the cyclin B1 expression. ...
Background
Cyclin B plays a crucial role in cancer cell cycle progression and is overexpressed in many human cancers, including breast cancer. However, the prognostic value of cyclin B expression in breast cancer is controversial. We performed a meta-analysis to assess the clinicopathological and prognostic significance of cyclin B expression in breast cancer.
Methods
We searched PubMed, web of science, and Embase databases to retrieve the publications investigating the association between cyclin B expression and clinicopathological/prognostic significance in breast cancer patients. The pooled hazard ratio (HR) or odds ratio (OR) with its 95% confidence intervals (CIs) were used to estimate the effects.
Results
Ten studies with 2366 breast cancer patients were included to evaluate the association between cyclin B expression and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and clinicopathological parameters. The results showed that cyclin B overexpression in breast cancer patients was significantly associated with both poor OS (univariate analysis: HR = 2.38, 95% CI = 1.72–3.30, P < .001), DFS (univariate analysis: HR = 1.86, 95% CI = 1.50–2.32, P < .001; multivariate analysis: HR = 1.75, 95% CI = 1.22–2.52, P = .003), and DSS (multivariate analysis: HR = 5.42, 95% CI = 2.15–13.66, P < .001). Additionally, cyclin B overexpression was significantly associated with lymphatic invasion (OR = 2.58, 95% CI = 1.03–6.46, P = .017).
Conclusion
Cyclin B overexpression appears to be an independent potential prognostic marker to DSS and DFS for breast cancer. Further studies with large sample size are needed to dissect the relationship between cyclin B and clinicopathological features or prognosis of breast cancer.
... Kaplan-Meier survival analyses showed that patients with high CCNB1 expression had worse OS than those with low CCNB1 expression, which is consistent with previous reports of CCNB1 in hypopharyngeal squamous cell carcinoma (11), liver cancer (12,33) and oesophageal cancer (34). However, Chae et al (35) did not detect any association of the expression of CCNB1 with the prognosis of patients with breast cancer. These inconsistent findings could potentially be explained by the different expression patterns of CCNB1 in different types of tumors. ...
... However, as there were no positive findings, CCNB1 appears to be a relatively independent expression factor. Similar findings have been reported in previous studies on breast cancer (35), pediatric embryonic tumors (11) and pancreatic cancer (36). However, some studies have identified associations between CCNB1 and clinical factors in LUAD. ...
Although great progress has been made in the early diagnosis and targeted therapy of lung adenocarcinoma (LUAD), the survival of patients with LUAD remains unsatisfactory. There is an urgent requirement for new biomarkers to guide the diagnosis, prognosis and treatment of LUAD. Following an initial bioinformatics screen, the present study focused on cyclin B1 (CCNB1) in LUAD. A total of 94 patients with LUAD from a single hospital were included in the study. CCNB1 protein expression was detected and scored in 94 LUAD samples and 30 normal tissue samples by immunohistochemistry. The associations between CCNB1 expression and the clinicopathological features of the patients with LUAD were analyzed. Furthermore, the relationship between prognosis and the CCNB1 expression level was analyzed using Cox regression and survival analyses. Weighted gene co-expression network analysis and RNA-sequencing were also applied to identify the potential molecular mechanisms of CCNB1 in LUAD. CCNB1 was highly expressed in patients with LUAD and was associated with poor prognosis. It may affect the expression of CPLX1, PPIF, SRPK2, KRT8, SLC20A1 and CBX2 genes and function via different pathways. CCNB1 has the potential to become a novel prognostic target for LUAD.
... inhibitors (8)(9)(10), which are normally required in regulating cell growth. CDK1 encodes a Ser/Thr kinase that plays an essential part in the eukaryotic cell cycle and was widely found to be overexpressed in oral SCC (13), liver cell carcinoma (14), epithelial ovarian cancer (15), and breast cancer (15). In contrast, gene silencing of CDK1 has exhibited therapeutic potential in epithelial ovarian cancer (16), breast cancer (17), and malignant pleural mesothelioma (18). ...
... inhibitors (8)(9)(10), which are normally required in regulating cell growth. CDK1 encodes a Ser/Thr kinase that plays an essential part in the eukaryotic cell cycle and was widely found to be overexpressed in oral SCC (13), liver cell carcinoma (14), epithelial ovarian cancer (15), and breast cancer (15). In contrast, gene silencing of CDK1 has exhibited therapeutic potential in epithelial ovarian cancer (16), breast cancer (17), and malignant pleural mesothelioma (18). ...
Background:
Cutaneous squamous cell carcinoma (cSCC) is a relatively common cancer that accounts for nearly 50% of non-melanoma skin cancer cases. However, the genotypes that are linked with poor prognosis and/or high relapse rates and pathogenic mechanisms of cSCC are not fully understood. To address these points, three gene expression datasets were analyzed to identify candidate biomarker genes in cSCC.
Methods:
The GSE117247, GSE32979, and GSE98767 datasets comprising a total of 32 cSCC samples and 31 normal skin tissue samples were obtained from the National Center for Biotechnology Information Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified and underwent pathway enrichment analyses with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG). A putative DEG protein-protein interaction (PPI) network was also established that included hub genes. The expression of CDK1, MAD2L1, BUB1 ans CDC20 were examined in the study.
Results:
A total of 335 genes were identified, encompassing 219 found to be upregulated and 116 genes that were downregulated in cSCC, compared to normal tissue. Enriched functions of these DEGs were associated with Ephrin receptor signaling and cell division; cytosol, membrane, and extracellular exosomes; ATP-, poly(A) RNA-, and identical protein binding. We also established a PPI network comprising 332 nodes and identified KIF2C, CDC42, AURKA, MAD2L1, MYC, CDK1, FEN1, H2AFZ, BUB1, BUB1B, CKS2, CDC20, CCT2, ACTR2, ACTB, MAPK14, and HDAC1 as candidate hub genes. The expression of CDK1 are significantly higher in the cSCC tissues than that in normal skin.
Conclusions:
The DEGs identified in this study are potential therapeutic targets and biomarkers for cSCC. CDK1 is a gene closely related to the occurrence and development of cSCC, which may play an important role. Bioinformatics analysis shows that it is involved in the important pathway of the pathogenesis of cSCC, and may be recognized and applied as a new biomarker in the future diagnosis and treatment of cSCC.
... On the contrary, the percentage of G2 phase cells was increased from 12.16 ± 1.53, 9.63 ± 1.53 to 23.46 ± 3.08, 17.98 ± 2.38 and 75.83 ± 9.01, 36.8 ± 4.90 (P < 0.001) (Fig. 5a, b, c, d). It has been widely known that the protein Cyclin B1 is closely correlated with G2 phase arrest, we examed its expression in SF-268 and T-98G cells after treating with the flubendazole by immunocytochemistry (Fig. 5e, f) and western blotting 16 . We found that flubendazole downregulated the expression of Cyclin B1 and p-cdc2, while upregulated the expression of P53. ...
... control) G2/M phase, which triggered the mitosis. The repression of both cyclin B1 and cdc2 would lead to overriding p53mediated G2/M arrest 16,28 . Thus, we evaluated the expression of proteins which are involved in regulating cell cycle transition from G2 phase to M phase after treatment of flubendazole. ...
Flubendazole, FDA-approved anthelmintic, has been widely used in treating testinal parasites. In the recent years, Flubendazole has been reported to exert anticancer activities. On the other hand, little was known about the effects of Flubendazole on gliomas. Here we demonstrated a novel effect of flubendazole on glioma cells. We found that Flubendazole inhibited cell proliferation and promoted cell apoptosis of glioma cell lines in vitro, and suppressed tumor growth in xenograft models by intraperitoneal injection. However, Flubendazole might have no influence on cell migration. Mechanism study reaveled that Flubendazole caused cell cycle arrest in G2/M phase, which partly account for the suppressed proliferation. Consistently, Flubendazole induced P53 expression and reduced Cyclin B1 and p-cdc2 expression in glioma cells. In addition, Flubendazole promoted cell apoptosis by regulating the classical apoptosis protein BCL-2 expression. These observations suggest that Flubendazole exerts anti-proliferation and pro-apoptosis effects in Glioma through affecting the cell cycle and intrinsic apoptotic signaling, and indicate a novel utilization of Flubendazole in the treatment of Glioma.
... Hücre siklusu siklinler, siklin bağımlı kinazlar (SBK) ve siklin bağımlı kinaz inhibitörleri (SBKİ) gibi birçok genle düzenlenir (14). p16INK4a protein ailesinin bir üyesi olan, 9p21 kromozomunda kodlanan, SBK-4 ve SBK-6'yı inaktive eden üç eksondan oluşan bir tümör supresör gendir (15,16). ...
... p16 ve bcl-2 meme karsinomu patogenezinde önemli rol almaktadır (25). p16 meme kanserinde tümör progresyonunda ve prognozunda kullanılabilecek bağımsız prognostik bir faktördür (16). Geradts and Wilson'un 1996 yılında 104 meme karsinomlu olgu üzerinden yaptıkları çalışmada p16 nükleer grade, histolojik grade ve mitoz ile ilişkili bulunmamakla birlikte, hasta sağkalımını ve tedaviye cevabı tahminde önemli rol aldığı vurgulanmıştır (14). ...
Aim: Breast cancer is the most frequent cancer among women. The p16INK4a and bcl-2 genes are the two major pathways involved in control of the cell cycle. They also play key roles in breast carcinogenesis. In this study, we investigated the relationships between the histopathologic parameters in the "Modified Scarff- Bloom-Richardson" microscopic grading and expression of p16 and bcl-2 gene in cases with invasive ductal carcinoma. Methods: We examined 88 patients who were diagnosed with invasive ductal carcinoma between 2011 and 2013 in Haseki Educational and Research Hospital Pathology Department. Immunohistochemical staining for p16 and bcl-2 was performed. Results: Increased expression of p16 gene was statistically significantly related with increased tubule formation, pleomorfism, mitosis rate and histological grade (p=0.008, p=0.001, p=0.005, and p<0.001, respectively). We found a statistically significant relationship of the rise of the expression of bcl-2 gene with decreased mitosis rate and histological grade (p=0.026 and p=0.024, respectively). Conclusion: As a result, it was observed that there was a positive correlation between parameters included in Modified Scarff- Bloom-Richardson grading system with p16 in addition to negative correlation with bcl-2 expression. p16 and bcl-2 are important prognostic biomarkers in human breast cancer.
... Cdc2 overexpression occurs at high frequency in several types of cancer. 26 Because the above finding suggests Cdc2 may be involved in the phosphorylation of Ubc9, we next examine the effect of SAMe and MTA on Cdc2 expression. Both SAMe and MTA treatment resulted in a decrease of Cdc2 mRNA and protein levels after 24 hours in RKO cells by 50% (Fig. 5B). ...
... Our in vitro kinase findings verified this and showed that Cdc2 phosphorylated Ubc9 recombinant protein and that roscovitine, an inhibitor of Cdc2, was able to significantly reduce Cdc2-mediated phosphorylation (Fig. 5A). Cdc2 is implicated in the genesis and/or progression of breast cancers 26 and is overexpressed in the majority of diffuse large B cell lymphoma specimens. 33 To investigate whether SAMe and MTA's effect on Ubc9 protein may involve Cdc2, we examined the effect of SAMe and MTA on Cdc2 expression. ...
... Cdc2 overexpression occurs at high frequency in several types of cancer. 26 Because the above finding suggests Cdc2 may be involved in the phosphorylation of Ubc9, we next examine the effect of SAMe and MTA on Cdc2 expression. Both SAMe and MTA treatment resulted in a decrease of Cdc2 mRNA and protein levels after 24 hours in RKO cells by 50% (Fig. 5B). ...
... Our in vitro kinase findings verified this and showed that Cdc2 phosphorylated Ubc9 recombinant protein and that roscovitine, an inhibitor of Cdc2, was able to significantly reduce Cdc2-mediated phosphorylation (Fig. 5A). Cdc2 is implicated in the genesis and/or progression of breast cancers 26 and is overexpressed in the majority of diffuse large B cell lymphoma specimens. 33 To investigate whether SAMe and MTA's effect on Ubc9 protein may involve Cdc2, we examined the effect of SAMe and MTA on Cdc2 expression. ...
Unlabelled:
Ubiquitin-conjugating enzyme 9 (Ubc9) is required for sumoylation and is overexpressed in several malignancies, but its expression in hepatocellular carcinoma (HCC) is unknown. Hepatic S-adenosyl methionine (SAMe) levels decrease in methionine adenosyltransferase 1A (Mat1a) knockout (KO) mice, which develop HCC, and in ethanol-fed mice. We examined the regulation of Ubc9 by SAMe in murine liver and human HCC, breast, and colon carcinoma cell lines and specimens. Real-time polymerase chain reaction and western blotting measured gene and protein expression, respectively. Immunoprecipitation followed by western blotting examined protein-protein interactions. Ubc9 expression increased in HCC and when hepatic SAMe levels decreased. SAMe treatment in Mat1a KO mice reduced Ubc9 protein, but not messenger RNA (mRNA) levels, and lowered sumoylation. Similarly, treatment of liver cancer cell lines HepG2 and Huh7, colon cancer cell line RKO, and breast cancer cell line MCF-7 with SAMe or its metabolite 5'-methylthioadenosine (MTA) reduced only Ubc9 protein level. Ubc9 posttranslational regulation is unknown. Ubc9 sequence predicted a possible phosphorylation site by cell division cycle 2 (Cdc2), which directly phosphorylated recombinant Ubc9. Mat1a KO mice had higher phosphorylated (phospho)-Ubc9 levels, which normalized after SAMe treatment. SAMe and MTA treatment lowered Cdc2 mRNA and protein levels, as well as phospho-Ubc9 and protein sumoylation in liver, colon, and breast cancer cells. Serine 71 of Ubc9 was required for phosphorylation, interaction with Cdc2, and protein stability. Cdc2, Ubc9, and phospho-Ubc9 levels increased in human liver, breast, and colon cancers.
Conclusion:
Cdc2 expression is increased and Ubc9 is hyperphosphorylated in several cancers, and this represents a novel mechanism to maintain high Ubc9 protein expression that can be inhibited by SAMe and MTA.
... The p53 gene is involved in cell division, apoptosis, angiogenesis, and DNA replication in normal conditions. The association of p53 with CDK1-P2 and CDC2 retains cancer cells in the G 1 and G 2 stages of the cell cycle (Taylor and Stark, 2001;Chae et al., 2011). In fact, it can be considered as either an inhibitor or promoter of tumor cells. ...
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... It was previously thought that abnormal changes in the p16 INK4a gene were dominated by gene deletion, and point mutations were not the main cause of genetic changes. The overexpression rate of p16 INK4a is more prominent in tumors with higher malignancy, and it is more overexpressed in breast cancer [39]. Conversely, there have been reports of p16 INK4a downregulation in breast cancer [40]. ...
Simple Summary
Breast cancer emergencies have become a rapidly evolving field in medicine during the last ten years. Carcinogenesis is a multiparametric process that involves diverse factors such as genetic, environmental, or aging. Recent research that elucidates the tumor biology and molecular pathways that mediate cancer progression and drug resistance has led to the development of various molecular targeted therapies involving monoclonal antibodies, small molecule receptor tyrosine kinase inhibitors, and agents that block downstream signaling pathways in breast cancer.
Abstract
Triple negative breast cancer (TNBC) is a heterogeneous tumor characterized by early recurrence, high invasion, and poor prognosis. Currently, its treatment includes chemotherapy, which shows a suboptimal efficacy. However, with the increasing studies on TNBC subtypes and tumor molecular biology, great progress has been made in targeted therapy for TNBC. The new developments in the treatment of breast cancer include targeted therapy, which has the advantages of accurate positioning, high efficiency, and low toxicity, as compared to surgery, radiotherapy, and chemotherapy. Given its importance as cancer treatment, we review the latest research on the subtypes of TNBC and relevant targeted therapies.
... CDK1 was shown to be overexpressed in different types of cancer, including oral squamous cell carcinoma, breast cancer and epithelial ovarian cancer [21][22][23]. In our previous publication we presented data showing its upregulation in laryngeal squamous cell carcinoma [3,11]. ...
Alterations of the cell cycle checkpoints lead to uncontrolled cell growth and result in tumorigenesis. One of the genes essential for cell proliferation and cell cycle regulation is CDK1. This makes it a potential target in cancer therapy. In our previous study we have shown upregulation of this gene in laryngeal squamous cell carcinoma (LSCC). Here we analyze the impact of siRNA-mediated CDK1 knockdown on cell proliferation and viability, measured with cell growth monitoring and colorimetric test (CCK8 assay), respectively. We proved that a reduction of CDK1 expression by more than 50% has no effect on these cellular processes in LSCC cell lines (n=2). Moreover, using microarrays, we analyzed global gene expression deregulation in these cell lines after CDK1 knockdown. We searched for enriched ontologies in the group of identified 137 differentially expressed genes (>2-fold change). Within this group we found 3 enriched pathways: protein binding (GO:0005515), mitotic nuclear division (GO:0007067) and transmembrane receptor protein tyrosine kinase signaling pathway (GO:0007169) and a group of 11 genes encoding proteins for which interaction with CDK1 was indicated with the use of bioinformatic tools. Among these genes we propose three: CDK6, CALD1 and FYN as potentially dependent on CDK1.
... The CDC2 gene is related to the highly conserved protein CDK1, which functions as a serine/threonine kinase and is a key player in cell cycle regulation [28]. The CDC2 gene is also considered a cancer-related gene whose overexpression may play an important role in human breast carcinogenesis [29]. While little is known about the ZBTB8 gene, the same ZBTB family protein, ZBTB7A, has been implicated in high expression in cancer tissue and the breast cancer cell lines MDA-MB-231 and MCF-7 [30], suggesting that ZBTB8 may act as a transcriptional repressor or be involved in tumorigenesis. ...
Background
Recently, many computational methods have been proposed to predict cancer genes. One typical kind of method is to find the differentially expressed genes between tumour and normal samples. However, there are also some genes, for example, ‘dark’ genes, that play important roles at the network level but are difficult to find by traditional differential gene expression analysis. In addition, network controllability methods, such as the minimum feedback vertex set (MFVS) method, have been used frequently in cancer gene prediction. However, the weights of vertices (or genes) are ignored in the traditional MFVS methods, leading to difficulty in finding the optimal solution because of the existence of many possible MFVSs.
Results
Here, we introduce a novel method, called weighted MFVS (WMFVS), which integrates the gene differential expression value with MFVS to select the maximum-weighted MFVS from all possible MFVSs in a protein interaction network. Our experimental results show that WMFVS achieves better performance than using traditional bio-data or network-data analyses alone.
Conclusion
This method balances the advantage of differential gene expression analyses and network analyses, improves the low accuracy of differential gene expression analyses and decreases the instability of pure network analyses. Furthermore, WMFVS can be easily applied to various kinds of networks, providing a useful framework for data analysis and prediction.
... CCNB1, also known as CyclinB1, belongs to the highly conserved cyclin family and is signi cantly overexpressed in various malignant tumors. Over-expression of CCNB1 has been reported in breast [22], colorectal [23], lung [24], thyroid [25], prostate [26], pancreatic [27], stomach [28] and liver [19] cancers. CCNB1 plays most important role in mitotic cycle, in which it regulates the G2-M transition and cell proliferation [29]. ...
Objectives: Hepatocellular carcinoma (HCC) is a common malignant tumor severely scathing human health. As we all know, one of the main risk factors of HCC is chronic hepatitis B virus (HBV) infection, which involved in the oncogenesis of HCC through direct and indirect mechanisms such as inflammatory injury, integration into the host genome and interaction with some special target genes. This study aimed to identify these key genes potentially associated with HBV-related HCC by bioinformatics analyses.
Results: Total of 320 DEGs was identified between HBV-related HCC tissue samples and adjacent normal samples. These DGEs were strongly associated with several biological processes, such as retinol metabolism and steroid hormone biosynthesis. A PPI network was constructed and top six hub genes, including CDK1, CCNB1, CDC20, CDKN3, HMMR and MKI67, were determined. GEPIA online tool analysis validated the six key hub genes had the same expression trend as predicted in The Cancer Genome Atlas (TCGA) datasets. The overall survival and disease-free survival reflected that high expression of CDK1, CDC20, HMMR, MKI67 and CCNB1 significantly predicted poor prognosis, whereas CDKN3 expression has no statistical differences in overall survival.
Conclusion: The present study identified key genes and pathways involved in HBV-related HCC, which will improve our understanding of the mechanisms underlying the development and recurrence of HCC. The six identified genes might be potential biomarkers for the diagnosis and treatment of HBV-related HCC.
... The TREX-NCTF expression profiles in cancer tissues from older patients suggest their possible functions as oncogenes, not tumor suppressors, in normal tissues. A substantial number of transcription factors and kinases are reported to be both oncogenic and tumor suppressive, and paradoxically, the transcriptional activity of tumor suppressors has been shown to increase in various cancer cells [19][20][21][22][23] . With respect to the cellular senescence mechanism thought to be a fundamental tumor-suppressing process, there appears to be some programmed decline of nuclear trafficking related to aging, and TREXes and NCTF regulator(s) may behave as tumor suppressors with aging. ...
Nucleocytoplasmic trafficking (NCT) of macromolecules is a fundamental process in eukaryotes that requires tight controls to maintain proper cell functions. Downregulation of the classical NCT pathway in senescent cells has been reported. However, whether this is a hallmark that exists across all types of cellular senescence remains unknown, and whether the mRNA export machinery is altered during senescence has not been demonstrated. Here, we show that the global transcriptomic downregulation of both the TREX (transcription-export) machinery and classical NLS-dependent protein transport machinery is a hallmark of varying types of senescence. A gene set-based approach using 25 different studies showed that the TREX-NCT gene set displays distinct common downregulated patterns in senescent cells versus its expression in their nonsenescent counterparts regardless of the senescence type, such as replicative senescence (RS), tumor cell senescence (TCS), oncogene-induced senescence (OIS), stem cell senescence (SCS), progeria and endothelial cell senescence (ECS). Similar patterns of TREX-NCT gene downregulation were also shown in two large human tissue genomic databases, the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. We also found that early-stage cancer tissues show consistent age-related patterns of TREX-NCT enrichment, suggesting the potential significance of TREX-NCT genes in determining cell fate in the early stage of tumorigenesis. Moreover, human cancer tissues exhibit an opposite TREX-NCT enrichment pattern with aging, indicating that deviation from age-related changes in TREX-NCT genes may provide a novel but critical clue for the age-dependent pathogenesis of cancer and increase in cancer incidence with aging.
... Previous studies have demonstrated that cyclin B1 is a key molecule for G2-M phase transition during the cell cycle in CRC. Cyclin B1 and CDC2 were revealed to cooperate positively to play a role in the progression of breast carcinomas, as determined through immunohistochemical (IHC) staining [42]. Another study indicated that cyclin B1 was expressed in different time-window sections of G1 in malignant cancer cells [43]. ...
Studies have revealed that people with hyperglycemia have a high risk of colorectal cancer (CRC). Hyperglycemia may be responsible for supplying energy to CRC cells. However, the potential molecular mechanism for this association remains unclear. Furthermore, microRNA-9 (miR-9) has a tumor-suppressive function in CRC. Aberrant reduced expression of miR-9 is involved in the development and progression of malignancy caused by a high glucose (HG) concentration. In this study, we used an HG concentration to activate miR-9 downregulation in CRC cells. Our results indicated that miR-9 decreased the insulin-like growth factor-1 receptor (IGF1R)/Src signaling pathway and downstream cyclin B1 and N-cadherin but upregulated E-cadherin. The HG concentration not only promoted cell proliferation, increased the G1 population, and modulated epithelial-to-mesenchymal transition (EMT) protein expression and morphology but also promoted the cell migration and invasion ability of SW480 (low metastatic potential) and SW620 (high metastatic potential) cells. In addition, low glucose concentrations could reverse the effect of the HG concentration in SW480 and SW620 cells. In conclusion, our results provide new evidence for multiple signaling pathways being regulated through hyperglycemia in CRC. We propose that blood sugar control may serve as a potential strategy for the clinical management of CRC.
... Among the top DEGs, up-regulated expression of genes such as COL10A1, MMP1, MMP11, and BUB1; down-regulated expression of genes such as ADH1B, CIDEC, FABP4, AQP7, RBP4, CDO1, FIGF, and LPL were reported to be differentially expressed in breast and or other cancers by various authors using microarray profiling in western population [26][27][28][29][30][31][32][33][34][35][36][37][38] , showing concordance with the present study. In the present study, we found up-regulation of cell cycle genes such as BUB1, CCNA2, CCNB2, and CDC2; up-regulated expression of BUB1, CCNA2, CCNB2 and CDC2 has also been reported in breast 39,40 and several other cancers 41-46 using microarray and were found to be associated with poor prognosis of the disease 44,[47][48][49] . Overexpression of the above cell cycle genes may be contributing to the uncontrolled proliferation of the tumour cells and hence may serve as biomarkers and targets for therapy. ...
Breast cancer is the most common cancer among women globally. In India, the incidence of breast cancer has increased significantly during the last two decades with a higher proportion of the disease at a young age compared to the west. To understand the molecular processes underlying breast cancer in Indian women, we analysed gene expression profiles of 29 tumours and 9 controls using microarray. In the present study, we obtained 2413 differentially expressed genes, consisting of overexpressed genes such as COL10A1, COL11A1, MMP1, MMP13, MMP11, GJB2, and CST1 and underexpressed genes such as PLIN1, FABP4, LIPE, AQP7, LEP, ADH1A, ADH1B, and CIDEC. The deregulated pathways include cell cycle, focal adhesion and metastasis, DNA replication, PPAR signaling, and lipid metabolism. Using PAM50 classifier, we demonstrated the existence of molecular subtypes in Indian women. In addition, qPCR validation of expression of metalloproteinase genes, MMP1, MMP3, MMP11, MMP13, MMP14, ADAMTS1, and ADAMTS5 showed concordance with that of the microarray data; wherein we found a significant association of ADAMTS5 down-regulation with older age (≥55 years) of patients. Together, this study reports gene expression profiles of breast tumours from the Indian subcontinent, throwing light on the pathways and genes associated with the breast tumourigenesis in Indian women.
... Currently, the exact role of cell cycle regulatory protein, cyclin B1 in cancer cell growth development, progression and metastasis is not completely understood [62,63]. It has been shown that beneficial effects of imiquimod results from inhibition of cyclin B1-induced G2 cell cycle arrest and apoptosis in PC cells, in vitro and in vivo [64]. ...
Thienopyrimidines containing a thiophene ring fused to pyrimidine are reported to have a wide-spectrum of anticancer efficacy in vitro. Here, we report for the first time that thieno[3,2-d]pyrimidine-based compounds, also known as the RP series, have efficacy in prostate cancer cells. The compound RP-010 was efficacious against both PC-3 and DU145 prostate cancer (PC) cells (IC50 < 1 µM). The cytotoxicity of RP-010 was significantly lower in non-PC, CHO, and CRL-1459 cell lines. RP-010 (0.5, 1, 2, and 4 µM) arrested prostate cancer cells in G2 phase of the cell cycle, and induced mitotic catastrophe and apoptosis in both PC cell lines. Mechanistic studies suggested that RP-010 (1 and 2 µM) affected the wingless-type MMTV (Wnt)/β-catenin signaling pathway, in association with β-catenin fragmentation, while also downregulating important proteins in the pathway, including LRP-6, DVL3, and c-Myc. Interestingly, RP-010 (1 and 2 µM) induced nuclear translocation of the negative feedback proteins, Naked 1 and Naked 2, in the Wnt pathway. In addition, RP-010 (0.5, 1, 2 and 4 µM) significantly decreased the migration of PC cells in vitro. Finally, RP-010 did not produce significant toxic effects in zebrafish at concentrations of up to 6 µM. In conclusion, RP-010 may be an efficacious and relatively nontoxic anticancer compound for prostate cancer. Future mechanistic and in vivo efficacy studies are needed to optimize the hit compound RP-010 for lead optimization and clinical use.
... Hence, it serves as a tumour suppressor and our and earlier observations that it is significantly associated with ER + tumours (Fedele et al., 2010) suggest that it should be explored as a candidate therapeutic target for ER + breast cancer. The second of our key proteins, mitotic kinase CDK1, is known to accelerate critical processes required for mitosis (Enserink and Kolodner, 2010) and correlates with tumour grade (Chae et al., 2011). Moreover, inhibitors of the family members CDK4/6 have been FDA-approved for the treatment of metastatic breast cancer in a first-line setting (Bilgin et al., 2017). ...
Accurate breast cancer classification is vital for patient management decisions, and better tumour classification is expected to enable more precise and eventually personalized treatment to improve patient outcomes. Here, we present a novel quantitative proteotyping approach based on SWATH mass spectrometry and establish key proteins for breast tumour classification derived from proteotype data. The study was based on 96 tissue samples representing five breast cancer subtypes according to conventional classification. Correlation of SWATH proteotype patterns indicated groups that largely recapitulate these subtypes. However, the proteotype-based classification also revealed varying degrees of heterogeneity within the conventional subtypes, with triple negative tumours being the most heterogeneous. Proteins that contributed most strongly to the proteotype-based classification include INPP4B, CDK1, and ERBB2, which are associated with oestrogen receptor status, tumour grade, and HER2 status, respectively. While these three key proteins exhibited high levels of correlation between protein and transcript levels (R>0.67), general correlation did not exceed R=0.29, indicating the value of protein-level measurements of biomarkers and disease-regulated genes. Overall, our data shows how large-scale protein-level measurements by next-generation proteomics can lead to improved patient stratification for precision medicine.
... Currently, the exact role of cell cycle regulatory protein, cyclin B1 in cancer cell growth development, progression and metastasis is not completely understood [62,63]. It has been shown that beneficial effects of imiquimod results from inhibition of cyclin B1-induced G2 cell cycle arrest and apoptosis in PC cells, in vitro and in vivo [64]. ...
Thienopyrimidines are a versatile group of compounds that contain a biologically active pharmacophore and reported to have anticancer efficacy in vitro. Here, we report for the first time, that thieno[3,2-d]pyrimidine - based compounds, designated the RP series, have efficacy in prostate cancer cells. The lead compound, RP-010, was efficacious in PC3 and DU-145 prostate cancer (PC) cells (IC50< 1µM). The cytotoxicity of RP-010 was significantly lower in normal cells. RP-010 (0.5, 1, 2, and 4 µM) arrested prostate cancer cells in the G2 phase of the cell cycle, induced mitotic catastrophe and apoptotic signaling in both PC cell lines. Mechanistic studies suggested that RP-010 (1 and 2 µM) inhibits the wingless-type MMTV (Wnt)/β-catenin signaling pathway, mainly by inducing β-catenin fragmentation, while down regulating important proteins in the pathway, i.e. LRP-6, DVL3, and c-Myc. Interestingly, RP-010 (1 and 2 µM) induced the nuclear translocation of the negative feedback proteins, Naked 1 and Naked 2, in the signaling pathway. In addition, RP-010 (0.5, 1, 2, and 4 µM) significantly decreased the migration and invasiveness of PC cells in vitro. Finally, RP-010 did not produce significant toxic effects in zebrafish at concentrations up to 6 µM. In conclusion, RP-10 is a promising anticancer compound in metastatic prostate cancer and did not produce overt toxicity in an in vivo zebrafish model. Future mechanistic and efficacy studies are needed in-vivo to optimize the lead compound RP-010 for clinical use.
... 21,22 For CDK1, many research studies have reported its overexpression in cancers and that it acts as an adverse prognostic factor, and many kinds of CDK inhibitors have been developed. 23 In our study, BIRC5, KIF11, MAD2L1, and NDC80 were overexpressed in breast cancer compared to normal breast tissues, and overexpression of these genes was significantly correlated with unfavorable clinical outcome in breast cancer patients. The results of our research were consistent with other studies. ...
Background
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor clinical outcome and limited treatment options. Lacking molecular targets, chemotherapy is the main adjuvant treatment for TNBC patients.
Materials and methods
To explore potential therapeutic targets for TNBC, we analyzed three microarray datasets (GSE38959, GSE45827, and GSE65194) derived from the Gene Expression Omnibus (GEO) database. The GEO2R tool was used to screen out differentially expressed genes (DEGs) between TNBC and normal tissue. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery to identify the pathways and functional annotation of DEGs. Protein–protein interaction of these DEGs was analyzed based on the Search Tool for the Retrieval of Interacting Genes database and visualized by Cytoscape software. In addition, we used the online Kaplan–Meier plotter survival analysis tool to evaluate the prognostic value of hub genes expression in breast cancer patients.
Results
A total of 278 upregulated DEGs and 173 downregulated DEGs were identified. Among them, ten hub genes with a high degree of connectivity were picked out. Overexpression of these hub genes was associated with unfavorable prognosis of breast cancer, especially, CCNB1 overexpression was observed and indicated poor outcome of TNBC.
Conclusion
Our study suggests that CCNB1 was overexpressed in TNBC compared with normal breast tissue, and overexpression of CCNB1 was an unfavorable prognostic factor of TNBC patients. Further study is needed to explore the value of CCNB1 in the treatment of TNBC.
... A p53-dependent arrest occurring at the G 2 phase of the cell cycle is associated with a proteasome-dependent decrease in cyclin B1 protein levels (32,33). In addition, a p53-dependent increase in p21 protein levels is associated with a decrease in cyclin B1 protein levels (34,35). The results of the present study revealed that resveratrol was able to induce G 2 /M phase arrest in HeLa cells. ...
Numerous studies have demonstrated the apoptotic and anti-proliferative effects of resveratrol, a natural polyphenolic phytoalexin, on various cancer cell lines. However, the effects of resveratrol on the regulation of human cervical carcinoma, and the mechanisms underlying these effects, remain to be elucidated. In the present study, the potential mechanisms underlying the effects of resveratrol in HeLa cervical carcinoma cells were investigated. The results revealed that resveratrol inhibited proliferation and induced apoptosis in HeLa human cervical cancer cells in a dose-dependent and time-dependent manner. Resveratrol induced cell shrinkage in HeLa cells and apoptosis accompanied by the activation of caspase-3 and -9. Furthermore, resveratrol upregulated the expression of the pro-apoptotic B-cell lymphoma (Bcl)-2-associated X protein and downregulated the expression of the anti-apoptotic proteins Bcl-2 and Bcl-extra large in HeLa cells. In addition, p53, a protein that is essential for cell survival and cell cycle progression, exhibited elevated expression levels in resveratrol-treated HeLa cells. Therefore, resveratrol may be a promising novel inhibitor of human cervical cancer.
... Based on the clinical investigation, the overexpression of P16 is closely correlated with the infiltration of tumors into para-tissues in BC patients [25]. The result is also confirmed by the fact that the expression of P16 is significantly higher in invasive BCs that in non-invasive types [18]. ...
P16 is the product of cyclin-dependent kinase 2 (CDKN2A) gene and plays multi-pronged roles in the cancer progression. Breast cancer (BC) is the most commonly diagnosed cancer type among females. In the current study, the potential function of P16 in the growth and metastasis of BC was investigated. Firstly, the expression statuses of P16 in different cancer types were investigated using Oncomine database and validated with corresponding cancer cell lines. Afterwards, the expression of P16 was knocked down in BC cell line BT-549 and the effect on the cell proliferation, sensitivity to paclitaxel (TAX), apoptosis, migration, and invasion abilities was assessed using CCK-8, Edu, flow cytometry, scratch, and transwell assays, respectively. The influence of P16 inhibition and P16 overexpression on the activity of IL-6/JAK/STAT3 signaling was explored. Additionally, the effect of P16 inhibition on the tumor growth was verified with a BC xenograft mice model. The abnormal expression of P16 was detected in BC cell line BT-549 as well as colorectal cancer and osteosarcoma cell lines. The inhibition of P16 suppressed the cell proliferation, invasion, and migration abilities while induced the apoptosis and sensitivity to TAX in BT-549 cells. At molecular level, P16 knockdown inhibited the expression of IL6ST and Survivin, and the phosphorylation of JAK2 and STAT3. However, the induced expression of P16 in P16-knockdown BT-549 cells restored the activity of IL-6/JAK2/STAT3 pathway. The results of in vitro assays were confirmed with BC xenograft models: the inhibition of P16 decreased the tumor growth rate. Findings outlined in the current study demonstrated that the inhibition of P16 decreased the growth and metastasis potential of BC cells by inhibiting IL-6/JAK2/STAT3 signaling.
... According to current research, cyclin B1 is one of a family of proteins varying in their expression levels during the cell proliferation cycle [29][30][31][32]. Cyclin B1 has various roles in cell proliferation cycle, including cell differentiation, cell apoptosis, and the (tumor cell) distant metastasis [33][34][35][36][37]. Increasing proofs have indicated that the important protein was high or over expressed in laryngeal cancer [12], prostate cancer [9], pancreatic carcinoma [10], lung carcinoma [11], breast carcinoma [8], hepatocellular cancer [13], esophageal cancer, gastric cancer and colorectal cancer [15,20,23,24]. ...
Recently, several studies have reported that the expression of cyclin B1 may be associated with the prognosis of cancer. Nevertheless, their conclusions were still controversial. The present was designed to analyze and evaluate the prognostic role of cyclin B1 expression in patients with digestive cancer. PubMed, Embase, Cochrane Library and Web of Science were searched to January, 2017. Pooled odds ratio (OR) with 95% confidence intervals (CIs) were estimated. For the pooled OR estimates of OS, we performed subgroup analysis. Besides, sensitivity analysis was performed to examine the stability of the combined results. All statistical analyses were performed using standard statistical procedures provided in RevMan 5.2. A total of 12 studies (N = 2080 participants) were included for this meta-analysis. The positive/high expression of cyclin B1 had an obvious association with both 3-year overall survival (OR 0.21, 95% CI 0.12–0.37; P < 0.00001) and 5-year overall survival (OR 0.20, 95% CI 0.12–0.34; P < 0.00001) in esophageal cancer, and 5-year overall survival of colorectal cancer (OR 2.01, 95% CI 1.32–3.08; P = 0.001). This meta-analysis indicated that positive/high expression of cyclin B1 may have a close association with worse survival in patients with esophageal cancer, but better prognosis in patients with colorectal cancer.
... Additionally, the majority of mutations related to the p53 gene occur in the DNA-binding position, and the disability of genes is controlled by p53 for replication. Cooperation of p53 with CDK1-P2 and CDC2 keeps cancer cells in G1 and G2 phases of cell cycle (28,29) . In fact, p53 is either an inhibitor or a promoter of cancer cells. ...
Cancer in the broader sense refers to more than 277 different types of cancer disease. Scientists have identified different stage of cancers, indicating that several gene mutations are involved in cancer pathogenesis. These gene mutations lead to abnormal cell proliferation. Genetic disorders caused by heritance or inheritance factors have a pivotal role in the increase of cell growth. With the assistance of technological advances in bioinformatics and molecular techniques, additional information has been obtained that can be useful for early diagnosis and proper treatment The effects of drugs on patients with cancer can predict and even manage some aspects of side effects. In recent years, carcinogenesis mechanisms have been detected by molecular genetic studies. The results of these studies led to an improved understanding of the role of genetic disorders in cancer formation. In this study, our aim was to review molecular aspects of cancer.
... This is in line with previous results showed by Lian et al. in larynx cancer tissues compared to adjacent non-neoplastic tissues [17]. Besides, CDK1 overexpression in cancer was shown also for oral squamous cell carcinoma [42], breast cancer [43], epithelial ovarian cancer [39], and hepatocellular carcinoma [44]. ...
In this study, we analyzed the expression profile of four genes (CCNA2, CCNB1, CCNB2, and CDK1) in laryngeal squamous cell carcinoma (LSCC) cell lines and tumor samples. With the application of microarray platform, we have shown the overexpression of these genes in all analyzed LSCC samples in comparison to non-cancer controls from head and neck region. We have selected CDK1 for further analysis, due to its leading role in cell cycle regulation. It is a member of the Ser/Thr protein kinase family of proven oncogenic properties. The results obtained for CDK1 were further confirmed with the application of reverse transcription quantitative polymerase chain reaction (RT-qPCR) technique, Western blot, and immunohistochemistry (IHC). The observed upregulation of CDK1 in laryngeal squamous cell carcinoma has encouraged us to analyze for genetic mechanisms that can be responsible this phenomenon. Therefore, with the application of array-CGH, sequencing analysis and two methods for epigenetic regulation analysis (DNA methylation and miRNA expression), we tried to identify such potential mechanisms. Our attempts to identify the molecular mechanisms responsible for observed changes failed as we did not observe significant alterations neither in the DNA sequence nor in the gene copy number that could underline CDK1 upregulation. Similarly, the pyrosequencing and miRNA expression analyses did not reveal any differences in methylation level and miRNA expression, respectively; thus, these mechanisms probably do not contribute to elevation of CDK1 expression in LSCC. However, our results suggest that alteration of CDK1 expression on both mRNA and protein level probably appears on the very early step of carcinogenesis.
Electronic supplementary material
The online version of this article (doi:10.1007/s13277-016-4991-4) contains supplementary material, which is available to authorized users.
... In the triple negative breast cancer phosphorylated-CDC2 was down-regulated. This is a particularly interesting finding because CDC2 functions in conjunction with Cyclin B1 in the regulation of mitosis and stimulate cell cycle progression, a process that is dysregulated in breast cancer [28]. In HER2+ breast cancer, Cyclin E, WT1, NF-kBp65 and BCL6 were up-regulated, suggesting that these proteins are regulated by HER2 pathway. ...
Introduction:
Although HER2 and ER pathways are predominant pathways altered in breast cancer, it is now well accepted that many other signaling pathways are also involved in the pathogenesis of breast cancer. The understanding of these additional pathways may assist in identifying new therapeutic approaches for breast cancer.
Methods:
13 invasive ductal carcinoma tissues and 5 benign breast tissues were analyzed for the mRNA expression level of 1243 cancer pathway-related genes using SmartChip (WaferGen, CA), a real-time PCR-base method. In addition, the levels of 131 cancer pathway-related proteins and phosphoproteins in 33 paired breast cancers were measured using our innovative Protein Pathway Array.
Results:
Out of 1,243 mRNAs, 68.7% (854) were detected in breast cancer and 395 mRNAs were statistically significant (fold change >2) between benign and cancer tissues. Of these mRNAs, 105 only expressed in breast cancer tissues and 33 mRNAs only expressed in normal breast tissues. Out of 131 proteins and phosphoproteins, 68% (89) were detected in cancer tissues and 57 proteins were significantly differentiated between tumor and normal tissues. Interestingly, only 3 genes (CDK6, Vimentin and SLUG) showed decreases in both protein and mRNA. Six proteins (BCL6, CCNE1, PCNA, PDK1, SRC and XIAP) were differentially expressed between tumor and normal tissues but no differences were observed at mRNA levels. Analyses of mRNA and protein data using Ingenuity Pathway Analysis showed more than 15 pathways were altered in breast cancer and 6 of which were shared between mRNAs and proteins, including p53, IL17, HGF, NGF, PTEN and PI3K/AKT pathways.
Conclusions:
There is a broad dysregulation of various pathways in breast cancer both at protein levels and mRNA levels. It is important to note that mRNA expression does not correlate with protein level, suggesting different regulation mechanisms between proteins and mRNAs.
... CDK1 also has a clear influence upon apoptosis, with uncontrolled activation resulting in premature mitosis (and subsequent cell death), while also stimulating apoptotic pathways via the Bcl-2 proteins. Overexpression of CDK1 has been associated with more aggressive disease, tumour infiltration and shorter survival in breast carcinoma (Chae et al, 2011), colon cancer (Meyer et al, 2009), hepatocellular carcinomas (Ito et al, 2000) and mantle cell lymphoma (Hui et al, 2005). Although expression of CDK1 was found in the majority of our MPM samples, it had no prognostic value. ...
Background:
Malignant pleural mesothelioma (MPM) is an aggressive tumour originating in the thoracic mesothelium. Prognosis remains poor with 9- to 12-month median survival, and new targets for treatments are desperately needed.
Methods:
Utilising an RNA interference (RNAi)-based screen of 40 genes overexpressed in tumours, including genes involved in the control of cell cycle, DNA replication and repair, we investigated potential therapeutic targets for MPM. Following in vitro characterisation of the effects of target silencing on MPM cells, candidates were assessed in tumour samples from 154 patients.
Results:
Gene knockdown in MPM cell lines identified growth inhibition following knockdown of NDC80, CDK1 and PLK1. Target knockdown induced cell-cycle arrest and increased apoptosis. Using small-molecule inhibitors specific for these three proteins also led to growth inhibition of MPM cell lines, and Roscovitine (inhibitor of CDK1) sensitised cells to cisplatin. Protein expression was also measured in tumour samples, with markedly variable levels of CDK1 and PLK1 noted. PLK1 expression in over 10% of cells correlated significantly with a poor prognosis.
Conclusion:
These results suggest that RNAi-based screening has utility in identifying new targets for MPM, and that inhibition of NDC80, CDK1 and PLK1 may hold promise for treatment of this disease.
Background and purpose
White matter lesions (WMLs) are thought to cause damage to the blood–brain barrier, thereby aggravating bleeding after intravenous thrombolysis. However, the risk factors for symptomatic cerebral haemorrhage after thrombolysis are still unclear. This study explored the risk factors for bleeding in patients with severe WMLs after intravenous thrombolysis to prevent bleeding as soon as possible.
Methods
A large single-centre observational study conducted a retrospective analysis of intravenous thrombolysis in patients with severe WMLs from January 2018 to March 2021. According to whether symptomatic cerebral haemorrhage occurred, the patients were divided into two groups, and then statistical analysis was performed.
Results
After a retrospective analysis of the data of nearly 1000 patients with intravenous thrombolysis and excluding invalid information, 146 patients were included, of which 23 (15.8%) patients had symptomatic cerebral haemorrhage. Univariate analysis showed that a history of hypertension (20% vs 4.9%, p=0.024), hyperlipidaemia (38.7% vs 9.6%, p<0.001), the National Institutes of Health Stroke Scale (NIHSS) score before thrombolysis (median 17 vs 6, p<0.001), low-density lipoprotein levels (median 2.98 vs 2.44, p=0.011), cholesterol levels (mean 4.74 vs 4.22, p=0.033), platelet count (median 161 vs 191, p=0.031), platelet distribution width (median 15.2 vs 12.1, p=0.001) and sodium ion levels (median 139.81 vs 138.67, p=0.043) were significantly associated with symptomatic cerebral haemorrhage. Further multivariate logistic regression analysis showed that hyperlipidaemia (OR=9.069; 95% CI 2.57 to 32.07; p=0.001) and the NIHSS score before thrombolysis (OR=1.33; 95% CI 1.16 to 1.52; p<0.001) were comprehensive risk factors for symptomatic cerebral haemorrhage.
Conclusion
Hyperlipidaemia and the NIHSS score before thrombolysis are independent risk factors for bleeding after intravenous thrombolysis in patients with severe WMLs. Delaying the onset of white matter and preventing risk factors for bleeding will help improve the prognosis of cerebral infarction and reduce mortality. These risk factors need to be further evaluated in future studies.
Cancer is a widely spreading disease all over the world and the second most leading cause of mortality worldwide. In the broader sense cancer refers to more than 277 different types of diseases. Scientists have identified different stages of cancers, indicating several gene mutations which are involved in cancer pathogenesis. These gene mutations lead to abnormal cell proliferation. Genetic disorders caused byinheritance or inheritance factors have a pivotal role in the increase of cell growth.With the assistance of technological advances in molecular techniques and bioinformatics extra information can be obtained which can be useful for early diagnosis and proper treatment. In recent years, carcinogenesis mechanisms have been detected by molecular genetic studies. Consumption of fruits, vegetables, spices, cereals and pulses has been associated with lower incidence of cancer and other chronic diseases, but how these dietary agents and their active ingredients minimize these diseases, is not fully understood. Whether it is oranges, hops, water-lily, locorice, wax apple or mulberry, they are all connected by a group of aromatic ketones, called chalcones (1,3-diaryl-2-propen-1-ones). Chalcones are a group of polyphenolic compounds derived from plants which belong to the flavonoids family and owna wide variety of modulatory and cytoprotective functions. They have been linked with anti-bacterial, anti-fungal, anti-inflammatory, anti-oxidant, anti-cancer and anti-diabetic activities. Immunoblot assay showed that chalcone decreased the expression of cyclin B1, cyclin A and Cdc 2 protein, as well as increased the expression of p21 and p27.The current review, however, deals with the role of various chalcones in biologically, pharmacologically, and medicinally important entities.
We have previously reported that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion patterns obtained from locally advanced breast cancer (LABC) patients prior to neoadjuvant therapy predicted pathologic clinical response. Genomic analyses were also independently conducted on the same patient population. This retrospective study was performed to test two hypotheses: (1) gene expression profiles are associated with DCE-MRI perfusion patterns, and (2) association between long-term overall survival data and gene expression profiles can lead to the identification of novel predictive biomarkers.
We utilised RNA microarray and DCE-MRI data from 47 LABC patients, including 13 inflammatory breast cancer (IBC) patients. Association between gene expression profile and DCE-MRI perfusion patterns (centrifugal and centripetal) was determined by Wilcoxon rank sum test. Association between gene expression level and survival was assessed using a Cox rank score test. Additional genomic analysis of the IBC subset was conducted, with a period of follow-up of up to 11 years. Associations between gene expression and overall survival were further assessed in The Cancer Genome Atlas Data Portal.
Differences in gene expression profiles were seen between centrifugal and centripetal perfusion patterns in the sulphotransferase family, cytosolic, 1 A, phenol-preferring, members 1 and 2 (SULT1A1, SULT1A2), poly (ADP-ribose) polymerase, member 6 (PARP6), and metastasis tumour antigen1 (MTA1). In the IBC subset our analyses demonstrated that differential expression of 45 genes was associated with long-term survival.
Here we have demonstrated an association between DCE-MRI perfusion patterns and gene expression profiles. In addition we have reported on candidate prognostic biomarkers in IBC patients, with some of the genes being significantly associated with survival in IBC and LABC.
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