Search

Although it is the most widely used biomarker for prostate cancer, the use of prostate specific antigen (PSA) is controversial due to its limitations in specificity and sensitivity. The proteasome is a complex associated with cell proliferation and apoptosis, and the abnormity of these processes may lead to tumor occurrence. Previous studies have reported that proteasomal activity is associated with cancer progression and can be used in risk stratification. The purpose of the present study was thus to investigate the feasibility of proteasome activity as a biomarker for prostate cancer. Proteasome activity in vitro and in vivo was detected, along with the expression of the substrate proteins NF-κB inhibitor-a (IκB-α), Bcl-2-associated X (Bax) and p27. Chymotrypsin-like proteasomal activity was elevated by 70% in vitro and 23% in vivo, and the expression levels of the proteasome substrate proteins IκB-α, Bax and p27 were decreased in prostate cancer cells and prostate tumor xenografts compared with normal mouse prostate tissue. In conclusion, proteasomal chymotrypsin-like activity maybe a potential biomarker for prostate cancer, and may be suitable to supplement PSA in clinical application for prostate cancer diagnosis. [ABSTRACT FROM AUTHOR]

The Wnt signaling pathway is aberrantly activated in the majority of human colorectal tumors. β‑catenin, a key component of the Wnt signaling pathway, interacts with the T‑cell factor/lymphoid enhancer‑binding factor family of transcription factors and activates transcription of Wnt target genes. Sp5 is one of the Wnt target genes, and its expression is commonly upregulated in colon cancer cells. The present study demonstrates that the expression of Sp5 is not upregulated in the colon cancer cell line HCT116, in which Wnt signaling is constitutively activated. Furthermore, the results demonstrate that Sp5 has the potential to inhibit cell proliferation through upregulation of the cell cycle inhibitor p27. These findings suggest that HCT116 cells downregulate Sp5 to avoid p27‑mediated growth arrest. [ABSTRACT FROM AUTHOR]

The imbalance between cell proliferation and apoptosis was implicated to serve key roles in cancer pathogenesis. The characteristics of microRNAs (miRNAs/miRs) have attracted much attention in research focusing on cancer pathogenesis in recent years. miR-122-3p has been reported to be associated with a number of disease processes and pathogenesis, including lung cancer. The present study aimed to investigate the association of miR-122-3p expression level with cell proliferation and apoptosis in a lung cancer cell line. A549 cells were transfected with miR-122-3p to interrupt the expression of miR-122-3p. Subsequently, MTT and BrdU assay, and western blot were used to analyze the influence of miR-122-3p on lung cancer cell proliferation, cell viability and its underlying mechanism. The present study revealed that, by targeting p27, overexpression of miR-122-3p inhibited cell proliferation in lung cancer. Furthermore, the cell apoptosis analysis suggested that overexpression of miR-122-3p was able to inhibit cell apoptosis by targeting Forkhead box O. These findings suggest that miR-122-3p may be associated with the pathology and progression of lung cancer and be a new therapeutic target for this disease. [ABSTRACT FROM AUTHOR]

The protein 14-3-3ζ contributes important regulatory functions in several cellular processes via binding to phosphorylated serine/threonine residues, which promotes cell cycle progression, cell proliferation and anti-apoptosis in multiple types of cancer. The aim of the present study was to investigate the functions of 14-3-3ζ in cholangiocarcinoma (CCA) progression and elucidate the molecular mechanism of 14-3-3ζ expression-mediated protein kinase B (Akt) phosphorylation and chemosensitivity in CCA cells. In the present study, 14-3-3ζ expression was investigated in clinical specimens using immunohistochemistry and compared with the clinicopathological features of patients with CCA. The association between 14-3-3ζ and phosphorylated Akt (pAkt) was determined among the tissues of the same patients using bivariate correlation analysis. The effects of 14-3-3ζ suppression on CCA cell function and gemcitabine sensitivity were investigated using small interfering RNA (siRNA). It was identified that 14-3-3ζ expression was positively correlated with pAkt (P=0.013) and that increased expression of 14-3-3ζ and pAkt were significantly associated with poor overall survival rate and metastasis (P=0.025 and 0.006, respectively). Downregulation of 14-3-3ζ using siRNA in CCA cell lines decreased cell proliferation, resulting in the inhibition of pAkt activity and increasing the protein level of the cell cycle inhibitor p27. The suppression of 14-3-3ζ enhanced the inhibitory effect of gemcitabine on CCA cell proliferation by inducing apoptotic cell death. Taken together, the results of the present study indicated that 14-3-3ζ is a potential target for CCA and may serve as a novel therapeutic approach to enhance chemosensitivity in the treatment of CCA. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common type of primary bone cancer in children and adolescents, but its mechanism remains unclear. Musashi RNA-binding protein 1 (MSI1) is highly expressed in certain cancer types and functions as a putative progenitor/stem cell marker. In the present study, it was demonstrated that MSI1 expression in osteosarcoma tissue was higher compared with in the paraneoplastic tissue samples. Knockdown of MSI1 using shRNA in MG-63 and HOS cells inhibited cell proliferation in vitro and tumor formation in vivo, suggesting that MSI1 serves an essential role in osteosarcomagenesis. Further investigations demonstrated that the knockdown of MSI1 leads to the cell cycle arrest at G0/G1 phase, and the upregulation of p21 and p27 protein expression in osteosarcoma cells. Additionally, luciferase assays demonstrated that MSI1 can bind to the 3' untranslated regions of p21 and p27 mRNA. In conclusion, the results of the present study suggest that the knockdown of MSI11 can suppress cell proliferation of osteosarcoma by targeting p21 and p27 and subsequently inhibiting cell cycle progression. [ABSTRACT FROM AUTHOR]

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are a type of pancreatic tumor, which have been identified following improvements in diagnostic imaging. However, the malignant transformation of IPMN has been difficult to diagnose clinically. To date, the mechanisms driving the progression of IPMN to cancer remain to be fully elucidated. The present study focused on Stathmin 1 (STMN1), a protein that is associated with the development of various types of cancer. The expression of STMN1 was examined immunohistochemically in tissues from cases of IPMN. The correlation between the STMN1 staining and clinical pathological factors was evaluated, and the expression of STMN1, p27 and S-phase kinase-associated protein 2 (SKP2) were compared. High expression levels of STMN1 were significantly correlated with regions of malignancy, and was associated with high expression of SKP2, low expression of nuclear p27 and a high Ki-67 index. High expression levels of STMN1 and SKP2 were significantly correlated with the transformation of IPMN to carcinoma. In addition, within the regions of carcinoma, the expression of STMN1 was weak in regions of adenoma and high in the cancerous regions. It was concluded that the high expression of STMN1 contributed to tumor proliferation and malignant transformation in the patients with IPMN. These results suggested that characterization of the expression of STMN1 may be a promising approach for predicting malignant transformation of pancreatic intraductal papillary mucinous adenoma. [ABSTRACT FROM AUTHOR]

MicroRNA-33a (miR-33a) was previously identified as a lipid regulator that controls the cellular balance between cholesterol and fatty acid metabolism. However, its role in tumor progression is largely unknown. The present study identified that miR-33a acts as a tumor suppressor in melanoma cells. The present study revealed that miR-33a was downregulated in melanoma cells compared with mela-nocytes. Overexpression of miR-33a suppressed the colony formation of human melanoma SK-MEL-1 and WM-115 cells. Furthermore, a bromodeoxyuridine incorporation assay and anaphase analysis revealed that miR-33a inhibits melanoma cell proliferation. miR-33a overexpression inhibited p27 phos-phorylation and upregulated p27 expression. Additionally, the present study demonstrated that PCTAIRE1 was a direct target of miR-33a; miR-33a overexpression suppressed the luciferase activity of a reporter construct containing a 3'-untranslated region of PCTAIRE1 and downregulated PCTAIRE1 in melanoma cells. An overexpression of PCTAIRE1 reversed the miR-33a-induced p27 accumulation and tumor suppres-sive effects. In summary, the present findings offer novel mechanistic insights into miR-33a and its downstream target in melanoma cells. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are short regulatory RNAs that negatively modulate protein expression at the post-tran-scriptional level. Additionally, they have been associated with the pathogenesis of a number of types of cancer. In the current study, two target sites for miR-150 were determined within the 3'-untranslated region of p27Kip1 (hereafter referred to as p27) mRNA, and it was determined that ectopic overexpression of miR-150 led directly to p27 downregulation in cancer cells. These findings indicate that miR-150 may be a novel regulator of p27 expression. In the databases of the University of California, Santa Cruz (UCSC) and Match online, two common transcrip-tionfactors were identified for miR-150 andp27: Cooperates with myogenic proteins 1 (COMP1) and hepatocyte nuclear factor-4 (HNF-4). Using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), it was determined that p27 is involved in pathways regulated by the target genes of miR-150. Therefore, these results suggest that there may be a regulatory loop between COMP1 and HNF-4-miR-150-p27. Additional functional studies are required to understand the molecular basis for the formation of this circuit loop, and provide an insight into the development of innovative therapies targeting specific tumor markers. [ABSTRACT FROM AUTHOR]

Pleural malignant mesothelioma is a malignant tumor with a poor prognosis that is strongly associated with asbestos exposure during its development. Because there is no adequate treatment for malignant mesothelioma, investigation of its molecular mechanism is important. The ferritin light chain (FTL) is a subunit of ferritin, and its high expression in malignant tumors, including malignant mesothelioma, has recently been reported; however, its role in malignant mesothelioma is unclear. The purpose of the present study was to clarify the function of FTL in malignant mesothelioma. The expression levels of FTL in malignant mesothelioma were examined using the Cancer Cell Line Encyclopedia database and our previous data. The short interfering (si)RNA against FTL was transfected into two mesothelioma cell lines, ACC-MESO-1 and CRL-5915, and functional analysis was performed. Expression of p21, p27, cyclin-dependent kinase 2 (CDK2) and phosphorylated retinoblastoma protein (pRb) associated with the cell cycle were examined as candidate genes associated with FTL. The expression levels of the FTL mRNA were higher in malignant mesothelioma compared with other tumors in the Cancer Cell Line Encyclopedia database, and among other genes in our previous study. Reverse transcription-quantitative PCR and western blotting demonstrated suppression of FTL expression in two cell lines transfected with FTL siRNA compared with cells transfected with negative control (NC) siRNA. In the two cell lines transfected with FTL siRNA, proliferation was significantly suppressed, and cell cycle arrest was observed in the G1 phase. The levels of p21 and p27 were increased, while those of CDK2 and pRb were decreased compared with NC. However, no significant differences in invasion and migration ability were revealed between FTL siRNA-transfected cells and NC. In conclusion, FTL may increase the proliferative capacity of malignant mesothelioma cells by affecting p21, p27, CDK2 and pRb, and promoting the cell cycle at the G1 phase. [ABSTRACT FROM AUTHOR]

Prognostic markers for colorectal cancer (CRC) have not yet been fully investigated. Phosphatase and tensin homolog (PTEN), p27 and Cyclin D1 play significant roles in tumorigenesis and cell cycle regulation, and therefore require evaluation for their prognostic value in this disease. The aim of the present study was to assess the prognostic value of the single and combined expression of PTEN, p27 and Cyclin D1 in CRC patients. Protein expression levels of PTEN, p27 and Cyclin D1 were examined by immunohistochemistry from 61 patients with CRC in either stage II or III. In the CRC tissues, the frequencies of PTEN(-), p27(-) and Cyclin D1(+) expression were 42.62% (26/61), 32.79% (20/61) and 45.90% (28/61), respectively. Depletion of PTEN and p27 was more common with respect to stage III, low grade and lymph node metastasis compared with stage II, moderate grade and no lymph node metastasis (P<0.05). Cyclin D1-positive expression was frequently detected in CRC of stage III, with lymph node metastasis and deeper invasion (P<0.05). The depletion of PTEN was significantly correlated with the loss of p27 (P<0.001) and with the increased expression of Cyclin D1 (P<0.001). PTEN(-) and/or p27(-) expression was significantly correlated with Cyclin D1(+) expression (P<0.05). Combined PTEN(-)/p27(-)/Cyclin D1(+) expression was correlated with a significant decrease in overall survival time (P<0.05). Combined p27(-) and Cyclin D1(+) expression indicated a worse overall survival time than other combined expression patterns. These findings indicate that the single expression of PTEN(-), p27(-) and Cyclin D1(+) and the combined detection of p27(-) and Cyclin D1(+) may be used as prognostic markers for overall survival time in CRC. [ABSTRACT FROM AUTHOR]

The cyclin-dependent kinase inhibitor p27Kip1 has been suggested as a prognostic marker in prostate cancer. The aim of this study was to determine the clinical and prognostic role of p27 expression in hormone-naive prostate cancers. A tissue microarray containing samples from 4,699 prostate cancers with attached pathological, clinical follow-up and molecular data was analyzed for nuclear p27 expression by immunohistochemistry. p27 staining was negative in 18.6%, weak in 33.5%, moderate in 28.4% and strong in 19.5% of 3,701 interpretable cancer spots. Loss of p27 immunostaining was linked to tumors of low Gleason grade (P<0.0001) and ERG fusion-negative cancers (P<0.0001). p27 levels were not associated with other parameters, including tumor stage, nodal stage, preoperative prostate-specific antigen (PSA) levels, surgical margin status and cell proliferation (as measured by the Ki67 labeling index). p27 expression was also unrelated to clinical outcome in all cancers, as well as in the subsets of ERG fusion-positive and -negative cancers. Overall, the present data demonstrated that elevated p27 expression was often unrelated to prostate cancer phenotype. Furthermore, the lack of an effect of the p27 protein levels on PSA recurrence following radical prostatectomy indicated that factors other than p27 expression are likely to be the major determinants of prostate cancer recurrence. However, a subset of ERG-negative, low-grade tumors was frequently characterized by loss of p27, suggesting a role of this alteration for the development of these tumors. [ABSTRACT FROM AUTHOR]

Pleural malignant mesothelioma is a malignant tumor with a poor prognosis that is strongly associated with asbestos exposure during its development. Because there is no adequate treatment for malignant mesothelioma, investigation of its molecular mechanism is important. The ferritin light chain (FTL) is a subunit of ferritin, and its high expression in malignant tumors, including malignant mesothelioma, has recently been reported; however, its role in malignant mesothelioma is unclear. The purpose of the present study was to clarify the function of FTL in malignant mesothelioma. The expression levels of FTL in malignant mesothelioma were examined using the Cancer Cell Line Encyclopedia database and our previous data. The short interfering (si)RNA against FTL was transfected into two mesothelioma cell lines, ACC-MESO-1 and CRL-5915, and functional analysis was performed. Expression of p21, p27, cyclin-dependent kinase 2 (CDK2) and phosphorylated retinoblastoma protein (pRb) associated with the cell cycle were examined as candidate genes associated with FTL. The expression levels of the FTL mRNA were higher in malignant mesothelioma compared with other tumors in the Cancer Cell Line Encyclopedia database, and among other genes in our previous study. Reverse transcription-quantitative PCR and western blotting demonstrated suppression of FTL expression in two cell lines transfected with FTL siRNA compared with cells transfected with negative control (NC) siRNA. In the two cell lines transfected with FTL siRNA, proliferation was significantly suppressed, and cell cycle arrest was observed in the G 1 phase. The levels of p21 and p27 were increased, while those of CDK2 and pRb were decreased compared with NC. However, no significant differences in invasion and migration ability were revealed between FTL siRNA-transfected cells and NC. In conclusion, FTL may increase the proliferative capacity of malignant mesothelioma cells by affecting p21, p27, CDK2 and pRb, and promoting the cell cycle at the G 1 phase., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Kambara et al.)

Expression and clinical significance of micro-RNA-21, PTEN and p27 in cancer tissue of patients with non-small cell lung cancer (NSCLC) were investigated. In this study, cancer tissue and adjacent tissue specimens from 230 patients with NSCLC were collected from thoracic surgery department in Hubei Cancer Hospital from March 2010 to February 2016. The expression of miRNA-21, PTEN and p27 in cancer tissue and adjacent tissue of patients with NSCLC was detected by RT-PCR. Combined with clinical information, the correlation among miRNA-21, PTEN, p27 and clinical features of NSCLC was analyzed. The expression of miRNA-21, PTEN, p27 in NSCLC was significantly lower than that in adjacent tissue by RT-PCR (P<0.05). There was no significant difference in age, sex and course of disease (P>0.050), but there were differences in smoking, lymph node metastasis, TNM stage and differentiation degree classification (P<0.050). By comparing the 3-year survival rate in the group with high and low expression of miRNA-21, PTEN and p27, it was found that the 36-month survival rate of patients with high expression of miRNA-21 was 85.19% (P<0.05), and of patients with low expression of miRNA-21 it was 95.90% (P<0.05). The 36-month survival rate of patients with high expression of PTEN was 85.59% (P<0.05), of patients with low expression of PTEN it was 94.96% (P<0.05) and in patients with high expression of p27 it was 84.91% (P<0.05). The 36-month survival rate of patients with low expression of p27 was 94.35% (P<0.05). The survival rates of miRNA-21, PTEN and p27 low expression groups were significantly higher than those of high expression groups (P<0.05). In conclusion, the expression of miRNA-21, PTEN and p271 in cancer tissue of NSCLC patients was low. The three indexes have good diagnostic efficacy based on ROC curve analysis, and are expected to be excellent indexes for early clinical diagnosis and prognosis of NSCLC. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common type of primary bone cancer in children and adolescents, but its mechanism remains unclear. Musashi RNA-binding protein 1 (MSI1) is highly expressed in certain cancer types and functions as a putative progenitor/stem cell marker. In the present study, it was demonstrated that MSI1 expression in osteosarcoma tissue was higher compared with in the paraneoplastic tissue samples. Knockdown of MSI1 using shRNA in MG-63 and HOS cells inhibited cell proliferation in vitro and tumor formation in vivo , suggesting that MSI1 serves an essential role in osteosarcomagenesis. Further investigations demonstrated that the knockdown of MSI1 leads to the cell cycle arrest at G 0 /G 1 phase, and the upregulation of p21 and p27 protein expression in osteosarcoma cells. Additionally, luciferase assays demonstrated that MSI1 can bind to the 3' untranslated regions of p21 and p27 mRNA. In conclusion, the results of the present study suggest that the knockdown of MSI11 can suppress cell proliferation of osteosarcoma by targeting p21 and p27 and subsequently inhibiting cell cycle progression.

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are a type of pancreatic tumor, which have been identified following improvements in diagnostic imaging. However, the malignant transformation of IPMN has been difficult to diagnose clinically. To date, the mechanisms driving the progression of IPMN to cancer remain to be fully elucidated. The present study focused on Stathmin 1 (STMN1), a protein that is associated with the development of various types of cancer. The expression of STMN1 was examined immunohistochemically in tissues from cases of IPMN. The correlation between the STMN1 staining and clinical pathological factors was evaluated, and the expression of STMN1, p27 and S-phase kinase-associated protein 2 (SKP2) were compared. High expression levels of STMN1 were significantly correlated with regions of malignancy, and was associated with high expression of SKP2, low expression of nuclear p27 and a high Ki-67 index. High expression levels of STMN1 and SKP2 were significantly correlated with the transformation of IPMN to carcinoma. In addition, within the regions of carcinoma, the expression of STMN1 was weak in regions of adenoma and high in the cancerous regions. It was concluded that the high expression of STMN1 contributed to tumor proliferation and malignant transformation in the patients with IPMN. These results suggested that characterization of the expression of STMN1 may be a promising approach for predicting malignant transformation of pancreatic intraductal papillary mucinous adenoma.

MicroRNA-33a (miR-33a) was previously identified as a lipid regulator that controls the cellular balance between cholesterol and fatty acid metabolism. However, its role in tumor progression is largely unknown. The present study identified that miR-33a acts as a tumor suppressor in melanoma cells. The present study revealed that miR-33a was downregulated in melanoma cells compared with melanocytes. Overexpression of miR-33a suppressed the colony formation of human melanoma SK-MEL-1 and WM-115 cells. Furthermore, a bromodeoxyuridine incorporation assay and anaphase analysis revealed that miR-33a inhibits melanoma cell proliferation. miR-33a overexpression inhibited p27 phosphorylation and upregulated p27 expression. Additionally, the present study demonstrated that PCTAIRE1 was a direct target of miR-33a; miR-33a overexpression suppressed the luciferase activity of a reporter construct containing a 3'-untranslated region of PCTAIRE1 and downregulated PCTAIRE1 in melanoma cells. An overexpression of PCTAIRE1 reversed the miR-33a-induced p27 accumulation and tumor suppressive effects. In summary, the present findings offer novel mechanistic insights into miR-33a and its downstream target in melanoma cells.

MicroRNAs (miRNAs) are short regulatory RNAs that negatively modulate protein expression at the post-transcriptional level. Additionally, they have been associated with the pathogenesis of a number of types of cancer. In the current study, two target sites for miR-150 were determined within the 3'-untranslated region of p27 Kip1 (hereafter referred to as p27) mRNA, and it was determined that ectopic overexpression of miR-150 led directly to p27 downregulation in cancer cells. These findings indicate that miR-150 may be a novel regulator of p27 expression. In the databases of the University of California, Santa Cruz (UCSC) and Match online, two common transcription factors were identified for miR-150 and p27: Cooperates with myogenic proteins 1 (COMP1) and hepatocyte nuclear factor-4 (HNF-4). Using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), it was determined that p27 is involved in pathways regulated by the target genes of miR-150. Therefore, these results suggest that there may be a regulatory loop between COMP1 and HNF-4-miR-150-p27. Additional functional studies are required to understand the molecular basis for the formation of this circuit loop, and provide an insight into the development of innovative therapies targeting specific tumor markers.

Prognostic markers for colorectal cancer (CRC) have not yet been fully investigated. Phosphatase and tensin homolog (PTEN), p27 and Cyclin D1 play significant roles in tumorigenesis and cell cycle regulation, and therefore require evaluation for their prognostic value in this disease. The aim of the present study was to assess the prognostic value of the single and combined expression of PTEN, p27 and Cyclin D1 in CRC patients. Protein expression levels of PTEN, p27 and Cyclin D1 were examined by immunohistochemistry from 61 patients with CRC in either stage II or III. In the CRC tissues, the frequencies of PTEN(-), p27(-) and Cyclin D1(+) expression were 42.62% (26/61), 32.79% (20/61) and 45.90% (28/61), respectively. Depletion of PTEN and p27 was more common with respect to stage III, low grade and lymph node metastasis compared with stage II, moderate grade and no lymph node metastasis (P<0.05). Cyclin D1-positive expression was frequently detected in CRC of stage III, with lymph node metastasis and deeper invasion (P<0.05). The depletion of PTEN was significantly correlated with the loss of p27 (P<0.001) and with the increased expression of Cyclin D1 (P<0.001). PTEN(-) and/or p27(-) expression was significantly correlated with Cyclin D1(+) expression (P<0.05). Combined PTEN(-)/p27(-)/Cyclin D1(+) expression was correlated with a significant decrease in overall survival time (P<0.05). Combined p27(-) and Cyclin D1(+) expression indicated a worse overall survival time than other combined expression patterns. These findings indicate that the single expression of PTEN(-), p27(-) and Cyclin D1(+) and the combined detection of p27(-) and Cyclin D1(+) may be used as prognostic markers for overall survival time in CRC.

Oral squamous cell carcinoma (OSCC) accounts for >80% of head and neck malignancies. p21, p27 and survivin proteins are abnormally expressed in OSCC and have been previously reported to correlate with cell proliferation and apoptosis. However, the prognostic significance of p21, p27 and survivin remains controversial. The aim of the present study was to investigate the association of clinical parameters and prognosis with the levels of p21, p27 and survivin expression in patients with OSCC. The levels of the three biomarkers were evaluated by immunohistochemical staining in specimens from 110 patients with OSCC and each section was scored according to the percentage of positive tumor cells and staining intensity. Log-rank test and Cox proportional hazards regression were performed to assess the correlation between biomarkers and clinical events. The association between the immunoexpression of p21, p27 and survivin and clinical pathological variables were analyzed by the χ 2 test and a non-parametric analysis. The expression of p21 in patients with OSCC was found to correlate with the expression of p27 and survivin. The results of the current study revealed that the five-year survival rate was significantly lower in patients with high p21 expression. In addition, the expression of p27 also showed a negative correlation with the five-year survival rate of OSCC, but to a lesser extent. By contrast, the expression of survivin was not a prognostic factor for OSCC. A Kaplan-Meier analysis and Cox proportional hazards model showed that lymph node metastasis and p21 expression were independent prognostic factors of OSCC.

Gastric cancer and cholangiocarcinoma are problematic throughout the world due to their destructive malignancy. In attempts to treat cholangiocarcinoma and gastric cancer, researchers often explore the effects of transforming growth factor-β1 (TGF-β1). TGF-β1 plays a crucial role in causing cell cycle arrest and fibrosis in cancer cells. The present study aimed to identify whether TGF-β1 is capable of functioning as an antitumor agent in two cancer cell lines; cholangiocarcinoma and gastric cancer. The downregulation of cyclin dependent kinase (cdk) 4 and the upregulation of p27 were investigated, in order to identify possible antitumor functions of TGF-β1. A number of different methods were implemented, including cell proliferation assay, bicinchoninic acid (BCA) assay and western blot analysis with TGF-β1, AGS (human gastric cancer cell line) and SUN-1196 (human cholangiocarcinoma cell line). In the AGS study, cdk4 values decreased from 1.000 to 0.670 and then to 0.664, with increasing TGF-β1 concentrations of 0, 0.5 and 5 ng/ml, respectively. By contrast, p27 values increased from 1.000 to 1.391 and then to 1.505, with increasing TGF-β1 concentrations of 0, 0.5 and 5 ng/ml, respectively. In the SUN-1196 study, p27 values increased from 0.548 to 0.807 and then to 0.844 with increasing TGF-β1 concentrations of 5, 25 and 50 ng/ml, respectively. Certain concentrations of TGF-β1 play antitumor roles in gastric cancer through the down-regulation of cdk4 and upregulation of p27. Certain TGF-β1 concentrations also have antitumor roles in cholangiocarcinoma through the upregulation of p27. With these results, we came a step closer to finding a cure for cholangiocarcinoma and gastric cancer.