AIM:To verify that CD markers are available for detecting cancer stem cell populations and to evaluate their clinical significance in colon cancer. METHODS:Immunohistochemistry for CD133, CD24 and CD44 was performed on the tissue microarray of 523 colorectal adenocarcinomas. Medical records were reviewed and clinicopathological analysis was performed. RESULTS:In colorectal adenocarcinoma, 128 of 523 cases (24.5%) were positive and 395 cases (75.5%) were negative for CD133 expression. Two hundred and sixty-four of 523 cases (50.5%) were positive and 259 cases (49.5%) were negative for CD24 expression. Five hundred and two of 523 cases (96%) were negative and 21 cases (4%) were positive for CD44 expression. Upon clinicopathological analysis, CD133 expression was present more in male patients (P = 0.002) and in advanced T stage cancer (P = 0.024). Correlation between CD24 expression and clinicopathological factors was seen in the degree of differentiation (P = 0.006). Correlation between CD44 expression and clinicopathological factors was seen in the tumor size (P = 0.001). Survival was not significantly related to CD133, CD24 and CD44 expression. C O N C L U S I O N :C D m a r k e r s w e r e r e l a t e d t o invasiveness and differentiation of colorectal adenocarcinoma. However, CD expression was not closely related to survival.

F emale breast cancer is a major public health problem, with more than 1 000 000 cases occurring worldwide annually. (1) Despite major advances that have been made in understanding the biological and clinical nature of the disease, the therapeutic problem persists. Therefore, identification of novel breast cancer biomarkers could be utilized as possible therapeutic targets or prognostic predictors that would contribute to the advancement of breast cancer treatment.Metastasis associated antigen 1 (MTA1) was originally identified by differential screening of a cDNA library from highly metastatic and non-metastatic rat mammary adenocarcinoma cell lines. (2)(3)(4) The expression level is estimated to be four-fold higher in the highly metastatic cell line MTLn3 than in the non-metastatic cell line MTC4. (2) The mRNA expression level of the human homolog of this gene is approximately four-times higher in a metastatic cell line (MDA-MB-231) than in a non-invasive and non-metastatic cell line (MDA-MB-468) in nude mice. (2) MTA1 is expressed physiologically at low levels in all normal tissue, except the testis. (2) Several studies have identified various roles for MTA1 in normal mammary gland development and human breast cancer progression, including cell proliferation and invasiveness. A study with MTA1 transgenic mice reveals that MTA1 dysregulation in mammary epithelium causes increased cell proliferation, hyper-branched ductal structure formation and precocious development, and results in the development of hyperplastic nodules and mammary gland tumors in virgin mice. (5) The growth of human MDA-MB-231 breast cancer cells is inhibited after treatment with MTA1 antisense phosphorothioate oligonucleotides. (6) MTA1 overexpression in non-invasive breast cancer MCF-7 cells yields larger colony formation in soft agar, augmented colony formation, as well as increased invasiveness in a Boyden chamber assay. (7) Thus, MTA1 may play an important role in tumorigenesis and tumor aggressiveness. However, the role of MTA1 in surgically resected breast cancer tissue with its clinicopathological parameters has not been investigated to date. Therefore, we analyzed the relationship between MTA1 expression and variable clinicopathological features.Tumor microenvironment is known to play an active role in tumor progression through adhesion molecules, angiogenesis and stromal host cells. (8)(9)(10) Previous experimental studies highlight the role of angiogenesis in tumor progression, such as tumor growth and blood-borne metastasis. (11,12) In breast cancer, the overall results of reported studies suggest that human breast cancer is an angiogenic-dependent tumor, and anti-angiogenic therapy may be beneficial for breast cancer patients. (13,14) Therefore, we analyzed the possible role of MTA1 in tumor angiogenesis of breast cancer by counting intratumoral microvessels, which is widely used to estimate tumor angiogenesis. (15) In the present study, we report a statistically significant correlation between MTA1 gene expression and increased...

Nuclear PTEN expression gradually decrease during the normal-adenoma-adenocarcinoma-metastasis sequence, which suggests an important role for PTEN in carcinogenesis. Moreover, loss of nuclear PTEN expression was a marker of poor clinical outcome in patients with stage II colorectal cancer.

HU may be a useful objective marker of bone remodeling in chronic rhinosinusitis.

Embryonic stem (ES) cells have the potential to differentiate into all three germ layers, providing new perspectives not only for embryonic development but also for the application in cell replacement therapies. Even though the formation of an embryoid body (EB) in a suspension culture has been the most popular method to differentiate ES cells into a wide range of cells, not much is known about the characteristics of EB cells. To this end, we investigated the process of EB formation in the suspension culture of ES cells at weekly intervals for up to 6 weeks. We observed that the central apoptotic area is most active in the first week of EB formation and that the cell adhesion molecules, except β-catenin, are highly expressed throughout the examination period. The sequential expression of endodermal genes in EBs during the 6-week culture correlated closely with that of normal embryo development. The outer surface of EBs stained positive for α-fetoprotein and GATA-4. When isolated from the 2-week-old EB by trypsin treatment, these endodermal lineage cells matured in vitro into hepatocytes upon stimulation with various hepatotrophic factors. In conclusion, our results demonstrate that endodermal cells can be retrieved from EBs and matured into specific cell types, opening new therapeutic usage of these in vitro differentiated cells in the cell replacement therapy of various diseases. Stem Cells 2005;23:817-827

Leptin, the product of the ob gene, is an adipocyte-derived neurohormone that regulates body fat storage and feeding behavior. Some studies have suggested that leptin has growth-factor-like functions in epithelial cells and its abnormal expression may be involved in cancer development and progression. We investigated leptin expression in normal and neoplastic colorectal tissues and its association with clinicopathological features and clinical outcome in colorectal adenocarcinoma patients. Leptin expression was evaluated on the tissue microarray of 44 normal colon mucosal tissues, 44 adenomatous polyps, and 437 colorectal adenocarcinomas by immunohistochemistry. Data were analyzed by chi-square test, one-way analysis of variance (ANOVA), Cox regression hazards model, and log-rank test with Kaplan-Meier curves. Frequency of leptin expression was dramatically increased from normal colonic mucosa (2/44, 4.5%) to adenomas (13/44, 29.5%) and adenocarcinomas (321/437, 73.5%) as neoplastic progression. Interestingly, leptin expression was correlated with favorable tumor features in depth of invasion (p = 0.033), lymph node metastasis (p = 0.019), American Joint Committee on Cancer (AJCC) and Dukes' stage (p = 0.021 and p = 0.005, respectively), differentiation (p = 0.010), and lymphatic invasion (p = 0.003). In univariate survival analysis, patients with leptin-positive adenocarcinoma revealed better overall and disease-free survivals (p = 0.032 and p = 0.004, respectively, log-rank test). In multivariate survival analysis with Cox proportional hazards model, leptin expression was an independent prognostic marker of disease-free survival (p = 0.009). We conclude that leptin was gradually expressed during the normal-adenoma-adenocarcinoma sequence, suggesting an association in colorectal carcinogenesis. In addition, high leptin expression was an indicator of favorable tumor features and better survival of colorectal cancer patients.

Background/AimsChronic liver disease is a major widespread cause of death, and whole liver transplantation is the only definitive treatment for patients with end-stage liver diseases. However, many problems, including donor shortage, surgical complications and cost, hinder their usage. Recently, tissue-engineering technology provided a potential breakthrough for solving these problems. Three-dimensional (3D) printing technology has been used to mimic tissues and organs suitable for transplantation, but applications for the liver have been rare.MethodsA 3D bioprinting system was used to construct 3D printed hepatic structures using alginate. HepG2 cells were cultured on these 3D structures for 3 weeks and examined by fluorescence microscopy, histology and immunohistochemistry. The expression of liver-specific markers was quantified on days 1, 7, 14, and 21.ResultsThe cells grew well on the alginate scaffold, and liver-specific gene expression increased. The cells grew more extensively in 3D culture than two-dimensional culture and exhibited better structural aspects of the liver, indicating that the 3D bioprinting method recapitulates the liver architecture.ConclusionsThe 3D bioprinting of hepatic structures appears feasible. This technology may become a major tool and provide a bridge between basic science and the clinical challenges for regenerative medicine of the liver.

Hepatocellular carcinoma is one of the most lethal cancers worldwide. More accurate stratification of patients at risk is necessary to improve its clinical management. As epithelial-mesenchymal transition is critical for the invasiveness and metastasis of human cancers, we investigated expression profiles of 12 genes related to epithelial-mesenchymal transition through a real-time polymerase chain reaction. From a univariate Cox analysis for a training cohort of 128 hepatocellular carcinoma patients, four candidate genes (E-cadherin [CDH1], inhibitor of DNA binding 2 [ID2], matrix metalloproteinase 9 [MMP9], and transcription factor 3 [TCF3]) with significant prognostic values were selected to develop a risk score of patient survival. Patients with high risk scores calculated from the four-gene signature showed significantly shorter overall survival times. Moreover, the multivariate Cox analysis revealed that fourgene signature (P = 0.0026) and tumor stage (P = 0.0023) were independent prognostic factors for overall survival. Subsequently, the four-gene signature was validated in an independent cohort of 231 patients from three institutions, in which high risk score was significantly correlated with shorter overall survival (P = 0.00011) and disease-free survival (P = 0.00038). When the risk score was entered in a multivariate Cox analysis with tumor stage only, both the risk score (P = 0.0046) and tumor stage (P = 2.6 · 10 -9) emerged as independent prognostic factors. In conclusion, we suggest that the proposed gene signature may improve the prediction accuracy for survival of hepatocellular carcinoma patients, and complement prognostic assessment based on important clinicopathologic parameters such as tumor stage. (Cancer Sci 2010; 101: 1521-1528 H epatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the most common primary hepatic malignancy, being responsible for 80% of malignant tumors in adult livers. Moreover, its mortality is third among all cancers, behind only lung and colon cancer.(1) HCC is known for its endemic prevalence in Asia and Africa, and the incidence of HCC has doubled in the USA and Europe in the past four decades.(1-3) HCC is resistant to conventional chemotherapy and is rarely amenable to radiotherapy, (4) leaving this disease with no effective therapeutic options and a very poor prognosis. Although the major etiological agents have been identified, the molecular pathogenesis of HCC remains unclear.(5) It is therefore important to identify molecular targets to develop novel diagnostic, therapeutic, and preventive strategies.Epithelial-mesenchymal transition (EMT) is a key step during embryogenesis but also plays a critical role in cancer progression, through which epithelial cancers invade and metastasize. (6) Therefore, EMT-related pathways have been studied in relation to cancer management and drug resistance, for instance in breast cancer (7) and ovarian cancer. (8) The existence of EMT in vivo has been controversial due to its spatial and temporal heterogeneit...