Pseudogene CSPG4P12 inhibits colorectal cancer progression by attenuating epithelial-mesenchymal transition.

Colorectal cancer is one of the most common malignant cancers. Pseudogenes have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of pseudogene CSPG4P12 in colorectal cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of CSPG4P12 in colorectal cancer and explore the possible underlying mechanism. The difference of CSPG4P12 expression between colorectal cancer tissues and adjacent normal tissues was analyzed using the online Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Cell viability and colony formation assays were conducted to evaluate cell viability. Transwell and wound healing assays were performed to assess cell migration and invasion capacities. Western blot was used to measure the expression levels of epithelial-mesenchymal transition-related proteins. Colorectal cancer tissues had lower CSPG4P12 expression than adjacent normal tissues. The overexpression of CSPG4P12 inhibited cell proliferation, invasion, and migration in colorectal cancer cells. Overexpressed CSPG4P12 promoted the expression of E-cadherin, whereas it inhibited the expression of vimentin, N-cadherin, and MMP9. These findings suggested that CSPG4P12 inhibits colorectal cancer development and may serve as a new potential target for colorectal cancer.

Pseudogene CSPG4P12 inhibits colorectal cancer progression by attenuating epithelial-mesenchymal transition

Colorectal cancer is one of the most common malignant cancers. Pseudogenes have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of pseudogene CSPG4P12 in colorectal cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of CSPG4P12 in colorectal cancer and explore the possible underlying mechanism. The difference of CSPG4P12 expression between colorectal cancer tissues and adjacent normal tissues was analyzed using the online Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Cell viability and colony formation assays were conducted to evaluate cell viability. Transwell and wound healing assays were performed to assess cell migration and invasion capacities. Western blot was used to measure the expression levels of epithelial-mesenchymal transition-related proteins. Colorectal cancer tissues had lower CSPG4P12 expression than adjacent normal tissues. The overexpression of CSPG4P12 inhibited cell proliferation, invasion, and migration in colorectal cancer cells. Overexpressed CSPG4P12 promoted the expression of E-cadherin, whereas it inhibited the expression of vimentin, N-cadherin, and MMP9. These findings suggested that CSPG4P12 inhibits colorectal cancer development and may serve as a new potential target for colorectal cancer.

Lefty1 Ameliorates Post-infarction Fibrosis by Suppressing p-Smad2 and p-ERK1/2 Signaling Pathways.

Transforming growth factor-ß1 signaling pathways are known to involve in the development of post-infarction fibrosis, a process characterized by the aberrant activation, proliferation, and differentiation of fibroblasts, as well as the unbalanced turnover of extracellular matrix proteins. Recent studies have shown that Lefty1, a novel member of TGF-ß superfamily, acts as a brake on the TGF-ß signaling pathway in non-cardiac tissues. However, its role in myocardial infarction (MI)-induced fibrosis and left ventricular remodeling has not been fully elucidated. Here, for the first time, we reported that Lefty1 alleviated post-MI fibroblast proliferation, differentiation, and secretion through suppressing p-Smad2 and p-ERK1/2 signaling pathways in vivo and in vitro. In MI mice or TGF-ß1-treated neonatal rat cardiac fibroblasts (CFBs), the expression of Lefty1 was upregulated. Adenovirus-mediated overexpression of Lefty1 significantly attenuated TGF-ß1-induced CFBs' proliferation, differentiation, and collagen production. Using the adeno-associated virus approach, we confirmed that Lefty1 attenuates MI-induced cardiac injury, as evidenced by the decreased infarct size and preserved cardiac function. These results highlight the importance of Lefty1 in the prevention of post-MI fibrosis and may help identify potential targets for therapeutic intervention of cardiac fibrosis. Graphical abstract.

Exosomal­miR­10a derived from colorectal cancer cells suppresses migration of human lung fibroblasts, and expression of IL­6, IL­8 and IL­1ß.

MicroRNAs (miRs) carried in exosomes serve an important role in the pre­metastatic microenvironment and in intercellular interactions. However, the function of exosomal­miR­10a derived from primary colorectal cancer (CRC) cells on fibroblasts in the lung metastatic microenvironment of patients with CRC remains unclear. Reverse transcription­quantitative PCR was performed using samples from patients with CRC, and demonstrated that the expression levels of miR­10a were significantly lower in serum and cancer tissue samples from patients with CRC compared with in serum from healthy individuals and paired non­cancerous tissues, respectively. In addition, the expression levels of miR­10a were inversely associated with the invasion depth of CRC. Exosomal­miR­10a derived from CRC cells reduced the proliferative and migratory activities of primary normal human lung fibroblasts (NHLFs), and the expression levels of IL­6, IL­8 and IL­1ß in NHLFs. The present study provided insight into the phenotypic alterations of NHLFs induced by exosomal­miR­10a derived from CRC cells, which may aid understanding of the mechanism underlying the process of CRC lung metastasis.

Emerging Role of TRIM Family Proteins in Cardiovascular Disease.

Ubiquitination is one of the basic mechanisms of cell protein homeostasis and degradation and is accomplished by 3 enzymes, E1, E2, and E3. Tripartite motif-containing proteins (TRIMs) constitute the largest subfamily of RING E3 ligases, with >70 current members in humans and mice. These members are involved in multiple biological processes, including growth, differentiation, and apoptosis as well as disease and tumorigenesis. Accumulating evidence has shown that many TRIM proteins are associated with various cardiac processes and pathologies, such as heart development, signal transduction, protein degradation, autophagy mediation, ion channel regulation, congenital heart disease, and cardiomyopathies. In this review, we provide an overview of the TRIM family and discuss its involvement in the regulation of cardiac proteostasis and pathophysiology and its potential therapeutic implications.

Epigenetically Upregulated MicroRNA-602 Is Involved in a Negative Feedback Loop with FOXK2 in Esophageal Squamous Cell Carcinoma.

MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various tumorigenesis processes. In this study, our results revealed that miR-602 expression levels in tumor tissues and preoperative serum from esophageal squamous cell carcinoma (ESCC) patients were higher than those in non-tumorous tissues and healthy volunteers. miR-602 overexpression was closely related to lymph node metastasis and TNM stages and correlated short overall, and it acted as an independent prognostic marker of ESCC. The methylation status of the miR-602 gene indicated more frequent hypomethylation of the CpG sites located upstream of the miR-602 gene in the ESCC tissues than in the adjacent normal tissues, and the methylation status of miR-602 correlated inversely with its expression levels. Subsequently, miR-602 overexpression promoted ESCC proliferation and metastasis and regulated cell cycles in vitro and in vivo. Mechanistically, a dual-luciferase experiment validated that Fork head box (FOX)K2 (FOXK2) was a direct target of miR-602. More importantly, systemic delivery of formulated miR-602 antagomir could reduce tumor growth and increased FOXK2 protein expression in nude mice. This work provides novel insight into the molecular pathogenesis of ESCC.

Peroneus Longus Tendon Autograft is a Safe and Effective Alternative for Anterior Cruciate Ligament Reconstruction.

The ipsilateral peroneus longus tendon (PLT) was utilized as an autograft for anterior cruciate ligament (ACL) reconstruction of patients with acute ACL rupture and grade III medial collateral ligament (MCL) injury. We investigated the efficacy and safety of this alternative autograft compared with autologous hamstring tendon (HT). Biomechanical testing of the graft options was performed and compared with the native ACL. Thirty-eight patients with acute ACL ruptures and grade III MCL injuries were treated with ACL reconstruction with a doubled autologous PLT or quadrupled autologous HT. Knee stability and function was evaluated clinically with the Lachman test and KT-2000 arthometer as well as subjectively with functional scores. Effects on the donor ankle were evaluated by biomechanical testing. The ultimate tensile strengths of doubled PLT and quadrupled HT were significantly higher than that of the native ACL and the ultimate tensile strength of doubled PLT was comparable with that of quadrupled HT. There were no significant differences in clinical or functional scores between the two groups. There were no significant differences in pre- and postoperative biomechanical testing of the donor ankle. PLT is a suitable alternative autograft for an ACL reconstruction in patients with a concomitant grade III MCL injury without a significant biomechanical disadvantage to the ankle donor site.

miR-4317 suppresses non-small cell lung cancer (NSCLC) by targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2).

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. MicroRNAs (miRNAs) have been indicated as crucial actors in cancer biology. Accumulating evidence suggests that miRNAs can be used as diagnostic and prognostic markers for NSCLC. METHODS: The purpose of this study was to characterize and identify the novel biomarker miR-4317 and its targets in NSCLC. The expression of miR-4317 was analyzed by in situ hybridization (ISH) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effect of miR-4317 on proliferation was evaluated through 3-4,5-dimethylthiazol-2-yl-5-3-carboxymethoxyphenyl-2-4-sulfophenyl-2H-tetrazolium (MTS) and colony formation assays, and cell migration and invasion were evaluated through transwell assays. The expression of target proteins and downstream molecules was analyzed by qRT-PCR and western blot. Dual-luciferase reporter assay was used to assess the target genes of miR4317 in NSCLC cells. RESULTS: Our results demonstrated that miR-4317 was downregulated in NSCLC tissues and serum, particularly in lymph node metastasis and advanced clinical stage tissues. Kaplan-Meier survival analysis showed that NSCLC patients with high expression of miR-4317 exhibited better overall survival (OS). Enhanced expression of miR-4317 significantly inhibited proliferation, colony formation, migration and invasion, and hampered cycles of NSCLC cell lines in vitro. Our results suggested that miR-4317 functions by directly targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2). In concordance with in vitro studies, mouse xenograft, lung, and brain metastatic studies validated that miR-4317 functions as a potent suppressor miRNA of NSCLC in vivo. Systemically delivered agomiR-4317 reduced tumor growth and inhibited FGF9 and CCND2 protein expression. Reintroduction of FGF9 and CCND2 attenuated miR-4317-mediated suppression of migration and invasion in NSCLC. CONCLUSIONS: Our results indicate that miR-4317 can reduce NSCLC cell growth and metastasis by targeting FGF9 and CCND2. These findings provide new evidence of miR-4317 as a potential non-invasive biomarker and therapeutic target for NSCLC.

Antitumor Effect of GO-PEG-DOX Complex on EMT-6 Mouse Breast Cancer Cells.

OBJECTIVE: Doxorubicin (DOX) can be used to treat malignant tumors, but with multiple adverse effects. Graphene oxide-polyethylene glycol (GO-PEG) is a novel nanoscale carrier material and can elevate solubility and biocompatibility of drugs. This study prepared a GO-PEG-DOX complex, whose toxicity and antitumor effects were evaluated on mouse EMT-6 breast cancer cells. MATERIALS AND METHODS: GO-PEG-DOX complex was prepared for calculating the drug carrier rate of DOX on GO-PEG by MV approach. EMT-6 cells were treated with 40 µg/mL GO-PEG, 1 µg/mL DOX, or 40 µg/mL +1 µg/mL GO-PEG-DOX for 72 h of incubation. Cells without treatment were considered the control group. Cell survival rate and apoptotic rate were tested at different time points. RESULTS: GO-PEG and GO-PEG-DOX complex were successfully prepared with satisfactory solubility. After 72 h of incubation, EMT-6 cells after GO-PEG-DOX treatment had significantly higher survival rate than GO-PEG group (p < 0.05). All three treatment groups had significantly elevated apoptotic rates than control group (p < 0.05). GO-PEG-DOX group had much more apoptosis (p < 0.05 compared with DOX group). Moreover, with elongated treatment time, all groups showed decreased survival rate (p < 0.05). CONCLUSION: GO-PEG did not reduce the cytotoxicity of DOX on EMT-6 cells. GO-PEG-DOX complex can increase the water solubility and targeting sensitivity of DOX, with facilitating effects on DOX-induced tumor cell apoptosis.

Night Sleep Duration and Risk of Incident Anemia in a Chinese Population: A Prospective Cohort Study.

The purpose was to study the association between sleep duration and the prevalence of anemia in Chinese people. There were 84,791 participants (men: 79.1%; women: 20.9%) aged 18-98 years in the prospective study. We divided the participants into five categories based on the individual sleep duration: ≤5 h, 6 h, 7 h(reference), 8 h, and ≥9 h. Anemia was defined based on hemoglobin <12 g/dL for men and <11 g/dL for women. The Cox proportional hazards model was used to assess the association between sleep duration and anemia. During median follow-up of 7.9 years, 2698 cases of anemia had occurred. The HRand (95% CI) of anemia (7 h as the reference group) for individuals reporting ≤5 h, 6 h, 8 h, and ≥9 h were 1.23(1.04-1.45), 1.26(1.11-1.44), 1.04(0.92-1.16) and 1.42(1.08-1.86), respectively. It showed that there was a significant interaction on the risk of anemia between sleep duration and sex in the secondary analysis (p < 0.001).The significant association between long sleepduration and anemia was found in women (HR, 2.29; 95% CI, 1.56-3.37), not in men(HR, 0.90; 95% CI, 0.60-1.34). Both short and long night sleep duration were associated with increased risk of anemia.

HIF-1α Promotes Breast Cancer Cell MCF-7 Proliferation and Invasion Through Regulating miR-210.

OBJECTIVE: Many malignant tumors grow in hypoxic condition, which is associated with tumor growth, invasion, and metastasis. MicroRNAs are of great significance in the development of multiple malignant tumors. This study cultured breast cancer cell MCF-7 under the condition of different concentrations of oxygen, to test cell proliferation and invasion, and detect miR-210 expression, aiming to analyze the influence of hypoxia on breast cancer cell behaviors as well as miR-210 expressions. MATERIALS AND METHODS: Breast cancer cell MCF-7 was cultured under normoxia, hypoxia, or anaerobic conditions for 12, 24, or 48 hours. Cell proliferation was detected by MTT assay. Cell invasion and migration were tested by transwell assay. HIF-1α mRNA and miR-210 expressions were determined by real-time polymerase chain reaction. RESULTS: MCF-7 cell proliferation was gradually increased following time extension (p < 0.05). MCF-7 cell exhibited higher proliferation, invasion, and migration activities in hypoxic and anaerobic groups compared with those in normoxic group during the same time period. HIF-1α mRNA and miR-210 were significantly upregulated in anaerobic group compared with those in other groups (p < 0.05). HIF-1α mRNA and miR-210 were obviously elevated at 12, 24, and 48 hours (p < 0.05). CONCLUSION: MCF-7 cell proliferation was increased, invasion and migration were enhanced, with upregulated expression of HIF-1α mRNA and miR-210 in the hypoxic and anaerobic group following time extension.

Chaperonin containing TCP1 subunit 5 is a tumor associated antigen of non-small cell lung cancer.

Novel tumor antigens and their related autoantibodies have tremendous potential for early diagnosis of non-small cell lung cancer (NSCLC). In this study, we identify antigens from NSCLC tissue and autoantibodies in sera of patients with NSCLC using a modified proteomics-based approach. We seperated and identified four NSCLC-associated proteins extracted from the cytosol in tumor tissues by mini-two-dimensional gel electrophoresis, followed by Western blot and hybridization with individual sera for confirmation of antibody binding. Of the proteins we identified, we selected 58 kDa chaperonin containing TCP1(T-Complex Protein 1) subunit 5 (CCT5) for validation. Serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) were measured in all serum samples with an immunoluminometric assay and a receiver operating characteristic (ROC) curve was analyzed for autoantibodies against CCT5, CEA and CYFRA 21-1. The results show that CCT5 can induce an autoantibody response in NSCLC sera and show higher expression in NSCLC tissues by immunohistochemistry and Western blot. Anti-CCT5 autoantibody was found in 51% (23/45) of patients with NSCLC, but only 2.5% (1/40) in non-tumor individual controls. A receiver operating characteristic curve constructed with a panel of autoantibodies against CCT5 (AUC=0.749), CEA (AUC=0.6758), and CYFRA 21-1(AUC=0.760) show a sensitivity of 51.1% and 97.5% specificity in discriminating NSCLC from matched controls. These results indicate the potential utility of screening autoantibodies in sera, show that CCT5 could be used as a biomarker in cancer diagnosis.

Long Sleep Duration Is an Independent Risk Factor for Incident Atrial Fibrillation in a Chinese Population: A Prospective Cohort Study.

There is limited information on the relation between sleep duration and incident atrial fibrillation. We aimed to investigate this association in a Chinese population using cohort data from a study in Kailuan. The analysis included 87,693 participants (age range, 18-98 years) free of atrial fibrillation at the baseline survey. Participants were divided into three categories according to self-reported sleep duration: ≤6.0 hours, 7 hours (ref), ≥8.0 hours. Atrial fibrillation diagnosis was made on a standard 12-lead electrocardiogram and via self-reported history. Cox proportional hazards models were used to calculate hazard ratio (HR) and confidence interval (CI) for atrial fibrillation, according to sleep duration. During median follow-up of 7.89 (range, 6.36-8.57) years, 322 cases of atrial fibrillation had occurred. Using 7 hours of sleep as the reference group, multivariable adjusted HRs (95% CI) for atrial fibrillation were 1.07 (0.75-1.53), 1.0 (ref), and 1.50 (1.07-2.10), from lowest to highest category of sleep duration. Secondary analysis showed no evidence of interactions between sleep duration and sex and snoring on the risk of incident atrial fibrillation (p = 0.75/0.25). We conclude long sleep duration may be a potential predictor/marker for incident atrial fibrillation.

DNA methylation of METTL7A gene body regulates its transcriptional level in thyroid cancer.

DNA methylation is the best-studied epigenetic mechanism for regulating gene transcription and maintaining genome stability. Current research progress of transcriptional regulation by DNA methylation mostly focuses on promoter region where hypomethylated CpG islands are present transcriptional activity, as hypermethylated CpG islands generally result in gene repression. Recently, the DNA methylation patterns across the gene body (intragenic methylation) have increasingly attracted attention towards their role in transcriptional regulation and efficiency, due to the improvement of numerous genome-wide DNA methylation profiling studies. However, the function and mechanism of gene body methylation is still unclear. In this study, we revealed that the methylation level of METTL7A, a seldom studied gene, was downregulated in thyroid cancer compared to normal thyroid cells in vivo and in vitro. Moreover, we determined the methylation level of one CpG site at the exon of the METTL7A gene body impacted the transcriptional activity. Through generating a mutation of this CpG site (CG to CC) of METTL7A exogenous vector artificially in vitro, we observed higher RNA polymerase II recruitment and a declined enrichment of methyl-CpG binding protein-2 in gene body of METTL7A, in papillary thryoid cancer cells (BCPAP) compared to normal thryoid cells. Finally, we revealed that EZH2, a subunit of polycomb repressor complex 2, dominant in thyroid cancer, might be responsible for regulating gene body methylation of METTL7A. Our study depicted the DNA methylation patterns and the transcriptional regulatory mechanism of the gene body in thyroid cancer. Furthermore, this study provides new insight into potential future avenues, for therapies targeting cancer.

miR-769-5p suppressed cell proliferation, migration and invasion by targeting TGFBR1 in non-small cell lung carcinoma.

MicroRNAs (miRNAs) are key regulators of multiple cancers, including non-small cell lung carcinoma (NSCLC). The aim of this study was to determine the expression pattern of miR-769-5p in NSCLC and to investigate its biological role during tumorigenesis. We showed that miR-769-5p was significantly downregulated and predicted poor prognosis in NSCLC compared with corresponding normal tissues. We then investigated its function and found that miR-769-5p significantly inhibited cell proliferation, migration and invasion in vitro and reduced tumor growth and metastasis in vivo. Furthermore, we explored the molecular mechanisms by which miR-769-5p contributes to NSCLC suppression and identified TGFBR1 as a direct target gene of miR-769-5p. Finally, we showed that TGFBR1 had opposite effects to those of miR-769-5p on lung cancer cells, suggesting that miR-769-5p might inhibit lung tumorigenesis by silencing TGFBR1. Taken together, our results demonstrated that miR-769-5p plays a pivotal role in NSCLC by inhibiting cell proliferation, migration and invasion by targeting TGFBR1.

[Expression of BTG1 protein in laryngeal squamous cell carcinoma and its clinical significance].

OBJECTIVE: To investigate the expression of B-cell translocation gene 1 (BTG1) and to determine the relationship between BTG1 expression and clinicopathological features, biological behaviors in laryngeal squamous cell carcinoma. METHOD: Immunohistochemistry and Western blot were used to analyze BTG1 protein expression in 70 cases of laryngeal cancer and 35 cases of adjacent corresponding laryngeal mucosal tissues to illuminate the relationship between BTG1 expression and clinical factors. RESULT: The positive rate of BTG1 protein expression was 31.43% in laryngeal carcinoma tissues, significantly lower than 91.43% in the adjacent laryngeal tissues (P < 0.05). Western blot showed the relative expression of BTG1 protein between cancer lesion and adjacent tissue were 0.217 ± 0.032 and 0.918 ± 0.081, showing the difference with statistical significance (P < 0.05). The expression of protein was significantly correlated with the tumor invasion, lymph node metastasis, clinic stage and histological grade (P < 0.05 or P < 0.01), but not with sex, age and tumor location (P > 0.05) of patients with laryngeal cancer. CONCLUSION: The expression of BTG1 protein was decreased in laryngeal squamous cell carcinoma, suggesting that BTG1 gene may be closely associated with the carcinogenesis and the degree of malignancy. Detection of BTG1 expression may be useful in diagnosis, treatment and prognosis of laryngeal carcinoma.

Garlic-derived compound S-allylmercaptocysteine (SAMC) is active against anaplastic thyroid cancer cell line 8305C (HPACC).

BACKGROUND: Epidemiological and experimental carcinogenesis studies provide evidence that components of garlic have anticancer activity. OBJECTIVE: In this study, the apoptotic effects of Garlic-derived compound S-allylmercaptocysteine (SAMC) were investigated in 8305C human anaplastic thyroid carcinoma cells. METHODS: The cell line 8305C (HPACC) were treated with SAMC and the MTT assay, flow cytometry (FCM), electron microscope method were used to test cell cycle, inhibitory rate and morphologic changes respectively. RESULTS: HPACC-8305C cells were suppressed after exposure to SAMC of 0.02 mg/ml, 0.06 mg/ml, and 0.1 mg/ml for 48 h. Compared with the control, the difference was significant (P< 0.05). SAMC could induce apoptosis of the cells in a dose-dependent and non-linear manner and increase the proportion of cells in the G2/M phase. Compared with the control, the difference was significant in terms of the percentage of cells in the G2/M phase (P< 0.05). After exposure to SAMC at 0.02 mg/ml for 24 hours, HPACC-8305C cells showed typical morphologic change. CONCLUSIONS: SAMC inhibits the growth of HPACC-8305C cells by induction of apoptotic cell death and inhibit telomerase activity, which appears to account for its anti-cancer activity.

Combined therapy against recurrent and intracranial invasion of sinonasal hemangiopericytoma: A case report.

Sinonasal hemangiopericytoma (HPC) is a soft tissue tumor of vascular origin. Open surgical methods and endoscopic techniques are considered the standard treatments for sinonasal HPC. However, local recurrences resulting from residual tumors are common. Adjuvant radiotherapy and chemotherapy have also been used to treat HPC, however, the number of studies which have investigated effective adjuvant treatments in the literature are limited. The current study reports a 42-year-old male with recurrent and intracranial invasion of sinonasal HPC, diagnosed in Xuanwu Hospital (Beijing, China). The patient underwent multiple surgeries to remove the tumors, however, no adjuvant therapy was adopted during this period and the tumors reoccurred within 1 year. On admittance to Tangshan People's Hospital (Tangshan, China), the patient presented with limited mouth opening and chewing ability, and hearing loss. Under observation using an electron microscope, HPC usually consists of spindle-shaped cells with elongated nuclei and displays characteristic staghorn-like vascular channels. In the present case, immunohistochemical studies were performed on paraffin-embedded sections of the tumor. The tumor cells expressed CD34, CD68(+/-), epithelial membrane antigen, CD31, α-actin, desmin, CD99, S-100, B-cell lymphoma-2 and Ki-67 (30%), but were negative for creatine kinase. The patient was treated with intensity-modulated radiotherapy and adjuvant chemotherapy, which demonstrated efficacy. No recurrence and metastasis was observed at the 1 year follow-up subsequent to the combined therapy.

Serum GROß: a potential tumor-associated biomarker for colorectal cancer.

OBJECTIVE: This study aimed to confirm the potential of growth-related gene product ß (GROß) as a biomarker for colorectal cancer. We compared serum GROß levels in patients with colorectal cancer, healthy individuals and individuals with non-tumor diseases. METHODS: We measured serum GROß levels with enzyme-linked immunosorbent assay in patients with colorectal cancer (123 preoperative samples and 66 postoperative samples), 88 healthy controls and 125 individuals with other diseases. Serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were measured in all samples with an immunoluminometric assay. Statistical analyses were performed to determine associations between serum GROß levels and clinical parameters for colorectal cancer. A receiver operating characteristic (ROC) curve was analyzed for GROß, CEA and CA19-9. RESULTS: The serum GROß levels were much higher in patients with colorectal cancer (median: 96.15 pg/ml) than those in healthy controls (median: 43.28 pg/ml, P < 0.01) and other disease controls (median: 57.30 pg/ml, P < 0.01). Serum GROß levels in colorectal cancer were correlated positively with tumor-node-metastasis staging (P < 0.01) and the depth of infiltration (P < 0.05), but not with the histological grade, tumor embolus, lymph node metastasis, gross pathologic tumor type, or patient gender. The sensitivity and specificity of the assay for serum GROß were 56.1% (69/123) and 95.31% (203/213), respectively. The area under the ROC curve constructed with GROß (0.834) was larger than that constructed with CEA (0.739) or CA19-9 (0.676) for discriminating colorectal cancer from matched controls. CONCLUSION: These preliminary results suggested that the serum GROß level could be a useful biomarker for colorectal cancer diagnoses.

B cell translocation gene 1 reduces the biological outcome of kidney cancer through induction of cell proliferation, cell cycle arrest, cell apoptosis and cell metastasis.

The aim of the present study was to determine the expression and function of B cell translocation gene 1 (BTG1) in kidney carcinoma. Kidney samples were obtained from cancer lesions (n=85) and the adjacent normal tissue (n=40) in kidney cancer patients immediately following endoscopic biopsy. The effect of BTG1 overexpression was examined in vitro utilizing a human kidney cancer cell line, ACHN, stably transfected with a recombinant lentivirus (LeBTG1 cells) and compared to empty vector­transfected controls (LeEmpty). BTG1 protein expression was significantly lower in kidney cancer tissue biopsies compared to normal tissue, as measured by immunohistochemistry (34.1 vs. 77.8% of tissues; P<0.05) and western blotting (0.481±0.051 vs. 0.857±0.081; P<0.05). In vitro analyses revealed that LeBTG1 cells had a reduced survival fraction compared to control LeEmpty cells, with higher rates of apoptosis (16.6±2.5 vs. 6.1±0.7%; P<0.05). The proportion of LeBTG1 cells in G(0)/G(1) stage and S phase was also significantly different from LeEmpty cells (66.8±5.3 and 22.2±1.5% vs. 44.4±3.1 and 34.5±2.3%, respectively; P<0.05), and the migration and invasion of LeBTG1 cells was significantly impaired with respect to LeEmpty cells (74.0±9.0 and 53.0±7.0 vs. 118.0±15.0 and 103.0±13.0, respectively; P<0.05). These effects were accompanied by decreased protein expression of cyclin D1, B­cell lymphoma 2 and matrix metalloproteinase 9 in LeBTG1 cells (0.118±0.018, 0.169±0.015 and 0.207±0.027, respectively) compared to control LeEmpty cells (0.632±0.061, 0.651±0.063 and 0.443±0.042, respectively; P<0.05). Reduced BTG1 expression is associated with increased disease severity, suggesting it is a negative regulator of kidney cancer and can serve as a prognostic indicator. The results of the present study show that BTG1 protein levels were significantly reduced in kidney cancer biopsy specimens and were associated with disease progression and prognosis.