Tumor recurrence and metastasis are the most common reason for treatment failure. Metastasis-associate in colon cancer-1 (MACC1) has been identified as a metastatic and prognostic biomarker for ...colorectal cancer and other solid tumors. Aldehyde dehydrogenase 1 (ALDH1), a marker of cancer stem cells, is also associated with metastasis and poor prognosis in many tumors. However, the prognostic value of either MACC1 or ALDH1 in non-small cell lung cancer (NSCLC) is unclear. In this study, we explored the relationship between MACC1 and ALDH1 expression, as well as their respective associations with clinicopathological features, to determine if either could be useful for improvement of survival prognosis in NSCLC.
The expression levels of both MACC1 and ALDH1 in 240 whole tissue sections of NSCLC were examined by immunohistochemistry. Clinical data were also collected.
MACC1 and ALDH1 were significantly overexpressed in NSCLC tissues when compared to levels in normal lung tissues. Investigation of associations between MACC1 or ALDH1 protein levels with clinicopathological parameters of NSCLC revealed correlations between the expression of each with tumor grade, lymph node metastasis, and tumor node metastasis. The overall survival of patients with MACC1- or ALDH1-positive NSCLC tumors was significantly lower than that of those who were negative. Importantly, multivariate analysis suggested that positive expression of either MACC1 or ALDH1, as well as TNM stage, could be independent prognostic factors for overall survival in patients with NSCLC.
MACC1 and ALDH1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets, for NSCLC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recurrence and metastasis are the usual manifestations of treatment failure of epithelial ovarian carcinoma (EOC). Vasculogenic mimicry (VM; blood supply development often seen in highly aggressive ...cancers), aldehyde dehydrogenase 1 (ALDH1, cancer stem cell biomarker), KiSS-1 (suppressor of tumor metastasis), and metastasis associated in colon cancer-1 (MACC1) are all useful predictive factors for metastasis and prognosis in various cancers. In this study, we analyzed associations among VM, ALDH1, KiSS-1, and MACC1 in EOC, and their respective correlations with clinicopathological characteristics and survival in EOC.
Positive rates of VM, ALDH1, KiSS-1, and MACC1 in 207 whole EOC tissue samples were detected by immunohistochemistry. Patients' clinical data were also collected.
Levels of VM, ALDH1, and MACC1 were significantly higher, and levels of KiSS-1 significantly lower, in EOC tissues than in benign ovary tumors. Levels of VM, ALDH1, KiSS-1, and MACC1 were associated significantly with tumor/lymph node/metastasis (LNM) grade, implantation, and International Federation of Gynecology and Obstetrics (FIGO) stage, and with patients' overall survival (OS); whereas the KiSS-1+ subgroup had significantly longer OS than did the KiSS-1- subgroup. In multivariate analysis, high VM, ALDH1 or MACC1 levels, FIGO stage, implantation and low KiSS-1 levels were independently associated with shorter OS in patients with EOC.
VM and expressions of ALDH1, KiSS-1, and MACC1 represent promising markers for metastasis and prognosis, and potential therapeutic targets for EOC.
Metastasis and recurrence are the most common reasons for treatment failure of colorectal carcinoma (CRC). Vasculogenic mimicry (VM, blood supply formation often seen in highly aggressive tumors), ...Aldehyde dehydrogenase 1 (ALDH1, a biomarker of cancer stem cells), KAI1 (a suppressor gene of tumor metastasis) are all valuable factors for metastasis and prognosis in diverse human cancers. However, the correlation of VM, ALDH1, KAI1 and microvessel density (MVD) in CRC is unclear. In this study, we analyzed the correlations among VM, ALDH1, KAI1 and MVD, as well as their respective correlations with clinicopathological parameters and survival in CRC.
The level of VM, ALDH1, KAI1 and MVD in 204 whole tissue samples of CRC were examined by immunhistochemistry. Clinical data was also collected.
Levels of VM, ALDH1 and MVD were significantly higher, and levels of KAI1 significantly lower, in CRC tissues than in normal colorectal tissues. Levels of VM, ALDH1 and MVD were positively associated with invasion of depth, lymph node metastasis (LNM), distant metastasis and tumor-node-metastasis (TNM) stages, and negatively with patients' overall survival (OS). Levels of KAI1 was negatively correlated with invasion of depth, LNM, distant metastasis and TNM stages, and the KAI1 positive expression subgroup had significantly longer OS than did the KAI1- subgroup. In multivariate analysis, high levels of VM, ALDH1 and KAI1, as well as TNM stages were independently correlated with lower OS in patients with CRC.
VM, MVD and the expression of ALDH1 and KAI1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets for CRC.
Metastasis-associated in colon cancer 1 (MACC1) has been reported to promote tumor cell invasion and metastasis. Cancer stem cells and epithelial-mesenchymal transition (EMT) have also been reported ...to promote tumor cell proliferation, invasion, and metastasis. KiSS-1, a known suppressor of metastasis, has been reported to be down-regulated in various tumors. However, the associations of MACC1, CD44, Twist1, and KiSS-1 in colonic adenocarcinoma (CAC) invasion and metastasis remain unclear. The purpose of this study is to investigate the roles of MACC1, CD44, Twist1, and KiSS-1 in CAC invasion and metastasis and their associations with each other and with the clinicopathological characteristics of CAC patients.
Immunohistochemistry and multivariate analysis were carried out to explore the expression of MACC1, CD44, Twist1, and KiSS-1 in 212 whole-CAC-tissue specimens and the corresponding normal colon mucosa tissues. Demographic, clinicopathological, and follow-up data were also collected.
The results of this study showed MACC1, CD44, and Twist1 expression to be up-regulated, and KiSS-1 expression was down-regulated in CAC tissues. Positive expression of MACC1, CD44, and Twist1 was found to be positively correlated with invasion, tumor grades, and lymph- node-metastasis (LNM) stages and tumor-node-metastasis (TNM) stages for patients with CAC. Positive expression of KiSS-1 was inversely associated with invasion, tumor size, LNM stage, and TNM stage. The KiSS-1-positive expression group had significantly more favorable OS than did the KiSS-1-negative group. Univariate analysis indicated that overexpression of MACC1, CD44, and Twists1 was negatively associated with longer overall survival (OS) time, and there was a positive relationship between KiSS-1-positive expression and OS time for patients with CAC. Multivariate Cox analysis demonstrated that overexpression of MACC1, CD44, Twist1, and low expression of KiSS-1 and LNM and TNM stages were independent predictors of prognosis in patients with CAC.
The results in this study indicated that levels of expression of MACC1, CD44, Twist1, and KiSS-1 are related to the duration of OS in patients with CAC. MACC1, CD44, Twist1, and KiSS-1 may be suitable for use as biomarkers and therapeutic targets in CAC.
Objective. To explore the effect and mechanism of a new processing method of Codonopsis pilosula (CP) on the endocrine physique index in rats. Methods. The rats were randomly assigned into the ...control group, model group, CP group (3.75 g/kg crude drug), rice-fried CP group (3.75 g/kg crude drug), and honey-roasted CP group (3.75 g/kg), with 10 rats in each group. All rats were gavaged according to the body weight of 1 mL/100 g every morning for 3 weeks. The water extracts of different processed products of CP were given to the drug group, the blank group, and the model group which were given the same volume of normal saline during the experiment. The model group and each administration group were fed every other day and drank freely for 21 days, during which the weight was weighed every 2 days. The changes of the organ index; the contents of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), adrenocorticotropic hormone (ACTH), and cortisol (Cor); and the activity of sodium and potassium adenosine triphosphate (Na+K+-ATP) were measured by enzyme-linked immunosorbent assay (ELISA). The expression of aquaporin-1 (AQP1) and aquaporin-2 (AQP2) mRNA was detected by RT-PCR. Results. Effect on the organ index: the organ index of the control group, CP group, rice-fried group, and honey moxibustion group was higher compared to that of the model group, and the organ index of the honey moxibustion group was the highest (P<0.05). The level of cAMP and the ratio of cAMP/cGMP in the model group were significantly higher compared to those of the control group (P<0.05); CGMP in the model group decreased significantly (P<0.05). Compared with the model group, the level of cAMP in the CP group, rice-fried group, and honey moxibustion group decreased significantly, while the ratio of cGMP and cAMP/cGMP increased significantly (P<0.05). Compared with the CP group, rice-fried group, and honey moxibustion group, the level of cAMP and the ratio of cAMP/cGMP in the honey moxibustion group were lower compared to those in the other two groups, and the ratio of cGMP in the honey moxibustion group was higher compared to that in the other two groups (P<0.05). The contents of ACTH and Cor in the model group were significantly higher compared to those in the control group (P<0.05). Compared with the model group, the contents of ACTH and Cor in the CP group, rice-fried group, and honey moxibustion group were significantly lower compared to those in the model group (P<0.05). Compared with the CP group, rice-fried group, and honey moxibustion group, the contents of ACTH and Cor in the honey moxibustion group were higher compared to those in the other two groups (P<0.05). The content of the Na+K+-ATP enzyme in the model group was significantly higher compared to that in the control group (P<0.05). Compared with the model group, the content of the Na+K+-ATP enzyme in the CP group, rice-fried group, and honey moxibustion group decreased significantly (P<0.05). Compared with the CP group, rice-fried group, and honey moxibustion group, the content of the Na+K+-ATP enzyme in the honey moxibustion group was higher compared to that in the other two groups (P<0.05). The expression of AQP1 and AQP2 mRNA in the kidney tissue of the kidney yin deficiency model group was significantly higher compared to that of the control group (P<0 05). Compared with the model group, the expression levels of AQP1 and AQP2 mRNA in the renal tissue of rats in the CP group, rice-fried group, and honey moxibustion group decreased in different degrees (P<0.05). There was no statistical difference between the CP group, rice stir-frying group, and honey moxibustion group. Conclusion. This study proves that the new processing method of CP can improve the endocrine physique index of rats, enhance their organ quality, and regulate the disorder of water metabolism in kidney yin deficiency syndrome and has a certain therapeutic effect on kidney yin deficiency syndrome. Different new processing methods of CP have different effects on promoting endocrine physique indexes of rats. It is concluded that honey-roasted CP has the best effect on promoting spleen deficiency, which may be through glucose metabolism, amino acid metabolism, and nucleotide metabolism, increasing ATP energy metabolism, so as to strengthen the symptoms of spleen deficiency in rats. The experimental data of this study indicate that the effect of honey-roasted CP is better compared to that of other processed products, which provides an experimental basis for the rational clinical application of the new processed products.
Background:
To examine the expression level of procollagen-lysine2-oxoglutarate 5-dioxygenase 2 (PLOD2) in esophageal squamous cell carcinoma (ESCC) and analyze its correlation with ...clinicopathological parameters, in order to explore the mechanism of PLOD2 in regulating invasion and metastasis of ESCC.
Methods:
Immunohistochemistry was used to detect the expression level of PLOD2 in tumor tissues and paired adjacent tissues of 172 patients with ESCC, and the relationship between PLOD2 expression and clinicopathological parameters was analyzed. The deposition of collagen fibers in tumor was detected by Sirius red staining. The correlation between tumor stem cells and epithelial–mesenchymal transition (EMT) markers ZEB1 was analyzed by multivariate logistic regression.
Results:
The expression level of PLOD2 in tumor tissues of patients with ESCC (70.35%, 121/172) was significantly higher than that in paired adjacent tissues (29.65%, 51/172;
P
< .01). The positive expression rate of PLOD2 in ESCC was related to T classification, lymph node metastasis, and pathological tumor node metastasis of a tumor. The expression rates of ZEB1, CD44, and CD133 in ESCC were correlated with T classification, lymph node metastasis and pathological tumor node metastasis. Scarlet red staining showed that collagen fiber deposition in ESCC tissues with high expression of PLOD2 was significantly higher than that in tissues with low expression of PLOD2 (
P
< .01). A positive correlation was observed between the expression of PLOD2 and CD133, PLOD2 and CD44, and PLOD2 and N-cadherin (
P
< .01). Moreover, a negative correlation was noted between the expression of PLOD2 and E-cadherin (
P
< .01). The combined expression of PLOD2 and ZEB1 were independent prognostic factors for the total survival time of patients with ESCC.
Conclusion:
PLOD2 is highly expressed in ESCC and is closely related to tumor invasion and metastasis. The mechanism of PLOD2 for promoting invasion and metastasis of ESCC may be related to activation of the EMT signaling pathway to promote EMT and tumor stem cell transformation.
To explore the expression of Snail and Slug in primary cervical squamous cell carcinoma (CSCC) and their relationship with KAI1 expression.
The expressions of Snail, Slug, and KAI1 proteins were ...examined by immunohistochemistry in 154 specimens of CSCC tissues, 50 specimens of cervical intraepithelial neoplasm (CIN), and 40 specimens of normal cervical tissues.
The positivity rates of Snail, Slug, and KAI1 expression were 0%, 2.5%, and 95.0% in normal cervical tissues, 32.0%, 34.0% and 64.0% in CIN tissues, and 66.2%, 66.9%, and 43.5% in CSCC tissues, respectively, showing significant differences in the rates among the 3 groups (P<0.05). The expressions of Snail, Slug, and KAI1 were significantly correlated with the histological grades of the tumor, depth of invasion, lymph node metastasis, International Federation of Gynecology and Obstetrics (FIGO) stages, and postoperative survival time (P<0.05). The expressions of Snail and Slug were positively correlated (r=0.752, P<0.001), and both of them were negative
To investigate the presence of cancer stem cells (CSCs) exist in non-small cell lung cancer (NSCLC) and explore the relationship among the expressions of CD133, Notch1, and vascular endothelial ...growth factor (VEGF) and their relations with the clinicopathological parameters of the patients.
A total of 305 specimens of NSCLC and 80 normal lung tissue specimens were analyzed for CD133, Notch1, and VEGF protein expressions by immunohistochemical staining.
In NSCLC specimens, the positivity rates of CD133, Notch1, and VEGF were 48.9%, 43.9%, and 45.6%, respectively, significantly higher than those in normal lung tissues (10.0%, 15.0%, and 0%, respectively, P<0.01). The expression levels of CD133, Notch1, and VEGF proteins were significantly correlated with the tumor grades, lymph node metastasis, TNM stages, and postoperative survival time of the patients (P<0.01). A positive correlation was found among the expression levels of CD133, Notch1, and VEGF proteins. Kaplan-Meier survival analysis showed a significantl
Aims
This study was conducted to explore the function of microRNA‐141‐3p/cyclin‐dependent kinase 8 (miR‐141‐3p/CDK8) in regulating trastuzumab resistance of breast cancer cells.
Materials and Methods
...Microarray analysis was performed to screen microRNAs that are differentially expressed in wild type and trastuzumab‐resistant (TR) breast cancer cell lines. TargetScan helped predict the target gene of miR‐141‐3p. The regulatory relationship was confirmed through a luciferase reporter assay, quantitative reverse transcriptase polymerase chain reaction, and Western blot analysis. The MTT assay, transwell invasion assay, and wound scratch assay were performed to measure the proliferative, invasive, and migratory ability of breast cancer cells, respectively. Tumor cell xenografts in nude mice were conducted to observe the effect of miR‐141‐3p on trastuzumab resistance in breast cancer cells in vivo. The enzyme‐linked immunosorbent assay was used to detect protein secretion.
Results
miR‐141‐3p was downregulated in the drug‐resistant cell lines. CDK8 was proved to be a target gene of miR‐141‐3p. Transfection of miR‐141‐3p or CDK8 small interfering RNA (siRNA) reversed the resistance to trastuzumab in TR cell lines and suppressed cell invasion and migration. Dysregulation of transforming growth factor beta (TGF‐β) was detected when the expression of CDK8 was silenced by CDK8 siRNA, and downregulation of TGF‐β had a notable effect on reducing the phosphorylation of SMAD2/SMAD3.
Conclusion
miR‐141‐3p could restore the sensitivity to trastuzumab in breast cancer cells by repressing CDK8, which might regulate the phosphorylation levels of SMAD2/SMAD3 via TGF‐β.
Low expression were repressed in trastuzumab‐resistant breast cancer cell lines. Transfection of miR‐141‐3p could restore the sensitivity to trastuzumab of breast cancer cells through repressing CDK8, which might regulate the phosphorylation level of SMAD2/SMAD3 via transforming growth factor beta.
Thyroid hormone receptor interactor 13 (TRIP13) is an AAA+-ATPase that plays a key role in mitotic checkpoint complex inactivation and is associated with the progression of several cancers. However, ...its role in lung adenocarcinogenesis remains unknown. Here, we report that TRIP13 is highly overexpressed in multiple lung adenocarcinoma cell lines and tumor tissues. Clinically, TRIP13 expression is positively associated with tumor size, T-stage, and N-stage, and Kaplan-Meier analysis revealed that heightened TRIP13 expression is associated with lower overall survival. TRIP13 promotes lung adenocarcinoma cell proliferation, clonogenicity, and migration while inhibiting apoptosis and G2/M phase shift in vitro. Accordingly, TRIP13-silenced xenograft tumors displayed significant growth inhibition in vivo. Bioinformatics analysis demonstrated that TRIP13 interacts with a protein network associated with dsDNA break repair and PI3K/Akt signaling. TRIP13 upregulatesAktSer473 and downregulatesAktThr308/mTORSer2448activity, which suppresses accurate dsDNA break repair. TRIP13 also downregulates pro-apoptotic BadSer136 and cleaved caspase-3 while upregulating survivin. In conclusion, heightened TRIP13 expression appears to promote lung adenocarcinoma tumor progression and displays potential as a therapeutic target or biomarker for lung adenocarcinoma.
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•TRIP13 is highly overexpressed in lung adenocarcinoma cells.•TRIP13 expression is positively associated with tumor size, T-stage, and N-stage.•Heightened TRIP13 expression is associated with lower overall survival.•TRIP13 promotes proliferation and inhibits apoptosis and G2/M phase shift.•TRIP13 is involved in regulating dsDNA break repair and PI3K/Akt signaling.
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