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Several genes, important for development, are reduced or silenced in adulthood, and their abnormal expression has been related to the occurrence and development of malignant tumors. Human sine oculis homeobox homolog (SIX) proteins belong to the homeobox family and play important roles in the development of different organs. Importantly, SIXs are predicted to have chromatin-binding and DNA-binding transcription factor activity with reported roles in cancers. However, a comprehensive analysis of SIXs in colorectal cancers (CRCs) has not been performed.To explore the expression pattern of six SIX proteins in CRCs and their relationship with the clinicopathological parameters of CRC patients as well as investigate the potential utilization of SIXs as novel prognostic indicators in CRCs.The expression level of SIXs in normal tissues of different organs and related cancerous tissues was analyzed in the Human Protein Atlas. Kaplan-Meier Plotter and GEPIA2 were used to analyze the prognostic values of SIXs. To analyze the potential signaling pathways with SIX family involvement, LinkedOmics was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of SIX4-related genes. Subsequently, immunohistochemical experiments were performed on CRC tissues and adjacent normal tissues, and we examined the SIX4 expression level in 87 pairs of patients with tissue microarray. The relationship between SIX4 and clinicopathological parameters in CRC patients was tested using theThe RNA levels ofThe current results provided a comprehensive analysis of the expression and prognostic values of SIX family members in CRC. Among different SIXs, SIX4 plays an oncogenic role in CRC to promote the development of malignancy. In CRC, SIX4 mRNA and protein expression is higher than that in normal tissues and associated with shorter CRC patient survival, suggesting that SIX4 may be a potential therapeutic target for treatment of CRC patients.

Gastric cancer (GC) is the fifth most diagnosed cancer and the third leading cause of cancer-related death worldwide. Although progress has been made in diagnosis, surgical resection, systemic chemotherapy, and immunotherapy, patients with GC still have a poor prognosis. The overall 5-year survival rate in patients with advanced GC is less than 5%. The FOXO subfamily, of the forkhead box family of transcription factors, consists of four members, FOXO1, FOXO3, FOXO4, and FOXO6. This subfamily plays an important role in many cellular processes, such as cell cycle, cell growth, apoptosis, autophagy, stress resistance, protection from aggregate toxicity, DNA repair, tumor suppression, and metabolism, in both normal tissue and malignant tumors. Various studies support a role for FOXOs as tumor suppressors based on their ability to inhibit angiogenesis and metastasis, and promote apoptosis, yet several other studies have shown that FOXOs might also promote tumor progression in certain circumstances. To elucidate the diverse roles of FOXOs in GC, this article systematically reviews the cellular functions of FOXOs in GC to determine potential therapeutic targets and treatment strategies for patients with GC.

BACKGROUND Abnormal expression patterns of mucin 2 (MUC2) have been reported in a variety of malignant tumors and precancerous lesions. Reduced MUC2 expression in the intestinal mucosa, caused by various pathogenic factors, is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability. However, the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer (CRC) is not clear. AIM To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC. METHODS Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients, including both cancer tissues and adjacent normal tissues. Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2, diamine oxide (DAO), and D-lactate (D-LAC). The relationship between MUC2 expression and clinical parameters was calculated by the χ2 test or Fisher’s exact test. Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests. RESULTS Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues (54% vs 79%, P < 0.05), and it was correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis in CRC patients (P < 0.05). However, the serum level of MUC2 in CRC patients was higher than that in normal controls, and was positively associated with serum levels of human DAO (χ2 = 3.957, P < 0.05) and D-LAC (χ2 = 7.236, P < 0.05), which are the biomarkers of the functional status of the intestinal mucosal barrier. And the serum level of MUC2 was correlated with TNM stage, tumor type, and distant metastasis in CRC patients (P < 0.05). Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival. CONCLUSION MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.

Glutathione peroxidases (GPxs) belong to a family of enzymes that is important in organisms; these enzymes promote hydrogen peroxide metabolism and protect cell membrane structure and function from oxidative damage. Based on the establishment and development of the theory of the pathological roles of free radicals, the role of GPxs has gradually attracted researchers’ attention, and the involvement of GPxs in the occurrence and development of malignant tumors has been shown. On the other hand, the incidence of breast cancer in increasing, and breast cancer has become the leading cause of cancer-related death in females worldwide; breast cancer is thought to be related to the increased production of reactive oxygen species, indicating the involvement of GPxs in these processes. Therefore, this article focused on the molecular mechanism and function of GPxs in the occurrence and development of breast cancer to understand their role in breast cancer and to provide a new theoretical basis for the treatment of breast cancer.

Zinc finger E-box binding homeobox 1 (ZEB1, also termed TCF8 and δEF1) is a crucial member of the zinc finger-homeodomain transcription factor family, originally identified as a binding protein of the lens-specific δ1-crystalline enhancer and is a pivotal transcription factor in the epithelial-mesenchymal transition (EMT) process. ZEB1 also plays a vital role in embryonic development and cancer progression, including breast cancer progression. Increasing evidence suggests that ZEB1 stimulates tumor cells with mesenchymal traits and promotes multidrug resistance, proliferation, and metastasis, indicating the importance of ZEB1-induced EMT in cancer development. ZEB1 expression is regulated by multiple signaling pathways and components, including TGF-β, β-catenin, miRNA and other factors. Here, we summarize the recent discoveries of the functions and mechanisms of ZEB1 to understand the role of ZEB1 in EMT regulation in breast cancer.

Understanding cancer biology and the development of novel agents for cancer treatment has always been the goal of cancer researchers. However, the research and development of new drugs is hindered by its long development time, exorbitant cost, high regulatory hurdles, and staggering failure rates. Given the challenges involved drug development for cancer therapies, alternative strategies, in particular the repurposing of 'old' drugs that have been approved for other indications, are attractive. Itraconazole is an FDA-approved anti-fungal drug of the triazole class, and has been used clinically for more than 30 years. Recent drug repurposing screens revealed itraconazole exerts anti-cancer activity via inhibiting angiogenesis and multiple oncogenic signaling pathways. To explore the potential utilization of itraconazole in different types of malignancies, we retrieved the published literature relating to itraconazole in cancer and reviewed the mechanisms of itraconazole in preclinical and clinical cancer studies. Current research predicts the hedgehog signaling pathway as the main target by which itraconazole inhibits a variety of solid and hematological cancers. As clinical trial results become available, itraconazole could emerge as a new antitumor drug that can be used in combination with first-line antitumor drugs.

Background Oral squamous cell carcinoma (OSCC) is a solid tumor of squamous epithelial origin. Currently, surgery is still the main treatment for OSCC, with radiotherapy and chemotherapy as important adjuvant treatments. However, the problem of poor prognosis of OSCC patients still exists in clinical practice. To explore further potential biomarkers or treatment targets in OSCC patients, this study used a high-throughput gene expression database to study the potential molecular mechanisms of OSCC carcinogenesis. Methods The GEO database related to OSCC was searched and analyzed using GEO2R. Oncomine and the Human Protein Atlas were used to evaluate the expression level of differentially-expressed genes (DEGs). The cBioPortal dataset was used to analyze the mutations of the potential DEGs and patient survival. Results Three GEO datasets, GSE146483, GSE138206, and GSE148944, were downloaded and 7 DEGs were found in common in OSCC tissues. Using Oncomine and the Human Protein Atlas, ANXA1, IL1RN, and SPINK5 were decreased in cancer tissues, while protein levels of APOE and IFI35 were increased accordingly. Interestingly, low levels of ANXA1 and SPINKS were associated with the TNM stage of OSCC patients. No mutations in DEGs were found in OSCC patients, based on the cBioPortal dataset. Survival analysis indicated OSCC patients with high MSR1 had poor overall survival (OS), while low expression of CXCR4, ANXA1, IL1RN, and SPINK5 also predicted poor OS in OSCC patients. Conclusions Our findings uncovered 7 potential biomarkers of OSCC patients, with ANXA1 and SPINK5 serving as potential tumor suppressor genes in OSCC.

As important modulators in multiple physiological processes, microRNAs (miRNAs) have been reported in various malignant tumors, including breast cancer. The current study investigated the function of a new tumor suppressor microRNA, miR-488, and its molecular mechanism of metastasis in breast cancers. CCK8 and transwell assays revealed that the upregulated miR-488 level significantly inhibited the proliferation and migration of breast cancer cells. As a potential downstream gene, the mRNA and protein level of FSCN1 was suppressed by increased miR-488 and vice versa. Luciferase assay showed that miR-488 directly bind to the 3′UTR of FSCN1 and suppressed the translation process of FSCN1. The promoter region of miR-488 was directly bound by Notch3 and promoted the expression of miR-488 transcriptionally. Immunohistochemistry results revealed that in patients with breast cancer, the expression of Notch3 and were negatively correlated with the FSCN1 levels significantly. Therefore, the current finding predicted miR-488 as a tumor suppressor molecule in breast cancer, and demonstrated that Notch3/miR-488/FSCN1 axis is established and involved in regulating the metastasis of breast cancers, providing novel therapeutic targets for patients with breast cancers.

The dysfunction of long non-coding RNAs (lncRNAs), without protein-coding potential, has been implicated in drug resistance against treatment in various human diseases, especially in malignant tumors. As the most common-diagnosed female malignancy worldwide, breast cancer is also the second-leading cause of cancer-related mortality in women. Despite the improvement in neo-adjuvant therapy, endocrine therapy, molecular-targeted treatment, and chemotherapy, drug resistance to various treatment regimens is still quite prevalent. This article focused on the lncRNAs and their functions in drug resistance against breast cancer therapeutic agents, in order to develop new precise treatment strategies for patients with breast cancers. The discovery of lncRNA opened new doors to the molecular mechanisms of the biological processes, and has provided new pathways to regulate biochemical events. Thus, lncRNAs may be developed as a biomarker for the detection and/or prevention of breast cancer. Additionally, lncRNA-based approaches may provide an additional treatment modality in personalized medicine alone or in combination with existing tumor-directed interventions to improve patient outcomes. In conclusion, lncRNAs molecules may represent the "next generation" therapy option for breast cancer patients.

Objective. To investigate the expression patterns and prognostic values of STEAP family members in the occurrence and development of breast cancer. Materials and Methods. The Human Protein Atlas was used to analyze the expression level of STEAPs in human normal tissues and malignant tumors. ONCOMINE datasets were analyzed for the comparison of the STEAPs levels between malignant cancers and corresponding normal tissues. Kaplan-Meier plotter was used to analyze the prognostic value of STEAPs in breast cancer patients. Results. STEAPs were widely distributed in human normal tissues with diverse levels. Normally, it is predicted that STEAP1 and STEAP2 were involved in the mineral absorption process, while STEAP3 participated in the TP53 signaling pathway and iron apoptosis. The results from ONCOMINE showed downregulation of STEAP1, STEAP2, and STEAP4 in breast cancers. Survival analysis revealed that breast cancer patients with high levels of STEAP1, STEAP2, and STEAP4 had a good prognosis, while those with low expression had high overall mortality. Conclusion. STEAP1, STEAP2, and STEAP4 are predicted to be the potential prognostic biomarkers for breast cancer patients, providing novel therapeutic strategies for them.

// Hua-Tao Wu 1 , Jing Liu 1, 2 , Guan-Wu Li 3 , Jia-Xin Shen 4 , Yi-Teng Huang 5 1 Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, PR China 2 Chang Jiang Scholar’s Laboratory, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Shantou University Medical College, Shantou, PR China 3 Open Laboratory for Tumor Molecular Biology, Department of Biochemistry, The Key Lab of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, PR China 4 Department of Hematology, The First Affiliated Hospital of Shantou University Medical College, Shantou, PR China 5 Health Care Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, PR China Correspondence to: Hua-Tao Wu, email: htwu@stu.edu.cn Jing Liu, email: jliu12@stu.edu.cn Keywords: STAT, breast carcinoma, prognosis, Kaplan-Meier plot, transcription Received: December 08, 2016 Accepted: March 21, 2017 Published: March 31, 2017 ABSTRACT Signal Transducer and Activators of Transcription (STAT) is a set of transcription factors, involved in diverse cellular functions. Evidences from cell lines, mouse models and human tissues implicate these transcription factors in the oncogenesis of breast cancer. However, the diverse expression patterns and prognostic values of 7 STATs remain to be elucidated. In the current study, we mined the transcriptional and survival data of STATs in patients with breast carcinoma (BC) through ONCOMINE , bc-GenExMiner, Kaplan-Meier Plotter and cBioPortal. It was found that STAT1/2 were up-regulated, whereas STAT3/4/5A/5B were down-regulated in BC patients compared with the normal tissues. The expressions of STAT5A/5B/6 were correlated with decreased levels of histological differentiation. In survival analyses through the Kaplan-Meier plotter database, high transcription levels of STAT2/4/5A/5B/6 were associated with better relapse-free survival (RFS) in all BC patients. Conversely, high STAT3 predicted shorter RFS in BC patients, suggesting that STAT3 is potential targets for precision therapy to BC patients. These data also provided STAT5A/5B/6 as new biomarker for BC prognosis.

Aldehyde dehydrogenase 1 (ALDH1) consists of a family of intracellular enzymes, highly expressed in stem cells populations of leukemia and some solid tumors. Up to now, 6 isoforms of ALDH1 have been reported. However, the expression patterns and the identity of ALDH1 isoenzymes contributing to ALDH1 activity, as well as the prognostic values of ALDH1 isoenzymes in cancers all remain to be elucidated. Here, we studied the expressions of ALDH1 transcripts in gastric cancer (GC) compared with the normal controls using the ONCOMINE database. Through the Kaplan-Meier plotter database, which contains updated gene expression data and survival information of 876 GC patients, we also investigated the prognostic values of ALDH1 isoenzymes in GC patients. It was found that when compared with normal tissues, ALDH1A1 mRNA expression was downregulated, whereas ALDH1A3 and ALDH1B1 were upregulated in GC patients. In survival analyses, high ALDH1A1 and ALDH1B1 expressions were associated with better overall survival (OS) in all GC patients. In addition, high transcription activity of ALDH1A1 predicted better OS in gastric intestinal type adenocarcinoma, but not in diffuse gastric adenocarcinoma. GC patients with high mRNA level of ALDH1B1 showed better OS in gastric intestinal type, and worse OS in diffuse type. Oppositely, high transcription activities of ALDH1A2, ALDH1A3 and ALDH1L1 predicted worsen overall survival in GC patients, suggesting that these isoenzymes might be responsible mainly for the ALDH1 activities in GC. These data provides ALDH1A2, ALDH1A3 and ALDH1L1 as excellent potential targets for individualized treatment of GC patients.

Extracellular matrix (ECM) is an important component of tumor microenvironment and plays critical roles in cancer development and metastasis, in which collagen is the major structural protein. Collagen type I alpha 1 (COL1A1) is reportedly associated with the development of several human diseases. However, the functions and mechanisms of cellular expression of COL1A1 in breast cancer remain unknown. The purpose of this study is to investigate the cellular expression of COL1A1 in breast cancer cells and patients, and its role in the development and metastasis of breast cancer.The immunofluorescence staining was used to identify the cellular location of COL1A1 in breast cancer cell lines. Real-time PCR was applied to measuring the mRNA levels of COL1A1 and genes of interest. Wound healing and transwell assay were performed to evaluate the effect of COL1A1 on metastasis of breast cancer cells. 97 patients with breast cancer were recruited in this study for evaluating the correlation of COL1A1 with survival and clinicopathological parameters.COL1A1 was expressed in all examined breast cancer cells. Knockdown of COL1A1 inhibited metastasis of breast cancer cells, with a low-level of CXCR4, independent of the epithelial-mesenchymal transition (EMT) process. In patients with breast cancer, cellular expression of COL1A1 was associated with ER/PR expression and metastasis status. The increased COL1A1 level was associated with poor survival, especially in patients with ER+ breast cancer. Patients with a high-level of COL1A1 showed better cisplatin-based chemotherapy response.Cellular expression of COL1A1 could promote breast cancer metastasis. COL1A1 is a new prognostic biomarker and a potential therapeutic target for breast cancer, especially in ER+ patients.

In this study, we investigated chemical structure of Lycium barbarum polysaccharides and its modulatory effect on oxidative stress in high-fat mice. The polysaccharides mainly contained xylose and glucose. Little amount of rhamnose, mannose and galactose was observed. The Lycium barbarum polysaccharides had IR bands at 800-1200 cm(-1), 1450-1800 cm(-1), 2500-3000 cm(-1), and 3200-3600 cm(-1), which were distinctive absorptions of polysaccharides. Rats are fed with high-fat diet for 2 months. Results showed that blood and liver antioxidant enzymes activities and GSH level in model mice significantly decreased, and MDA level significantly increased (P

The purpose of this study was to investigate the immune and antioxidant activities of Glycyrrhiza glabra polysaccharides (GGP) in rats fed high-fat diet. The experiment was performed on four groups of growing Kunming mice. The results of the experiment showed a statistically significant decrease in serum antioxidant enzyme activities in high-fat group. Administration of GGP dose-dependently significantly enhanced immune and antioxidant enzyme activities in the GGP-treated mice compared to the high-fat model mice. It is concluded that GGP treatment can enhance immune activities, and reduce oxidative stress in high-fat mice.

In the title compound, [Cu(C(11)H(11)NO(3))(C(11)H(16)N(4))]·H(2)O, the Cu(II) atom is five-coordinate in a distorted square-pyramidal geometry. The basal positions are occupied by three donor atoms from the tridentate Schiff base ligand and by one N atom from a bis-(3,5-dimethyl-prazol-l-yl)methane ligand. The apical position is occupied by the N atom of the other ligand of this type. There are only van der Waals contacts in the crystal structure.