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Human Carcinomas (human + carcinoma)
Selected AbstractsContinuous perfusion microfluidic cell culture array for high-throughput cell-based assaysBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2005Paul J. Hung Abstract We present for the first time a microfluidic cell culture array for long-term cellular monitoring. The 10 × 10 array could potentially assay 100 different cell-based experiments in parallel. The device was designed to integrate the processes used in typical cell culture experiments on a single self-contained microfluidic system. Major functions include repeated cell growth/passage cycles, reagent introduction, and real-time optical analysis. The single unit of the array consists of a circular microfluidic chamber, multiple narrow perfusion channels surrounding the main chamber, and four ports for fluidic access. Human carcinoma (HeLa) cells were cultured inside the device with continuous perfusion of medium at 37°C. The observed doubling time was 1.4 ± 0.1 days with a peak cell density of ,2.5*105 cells/cm2. Cell assay was demonstrated by monitoring the fluorescence localization of calcein AM from 1 min to 10 days after reagent introduction. Confluent cell cultures were passaged within the microfluidic chambers using trypsin and successfully regrown, suggesting a stable culture environment suitable for continuous operation. The cell culture array could offer a platform for a wide range of assays with applications in drug screening, bioinformatics, and quantitative cell biology. © 2004 Wiley Periodicals, Inc. [source] Suppression of cyclic GMP-specific phosphodiesterase 5 promotes apoptosis and inhibits growth in HT29 cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2005Bing Zhu Abstract Phosphodiesterase 5 (PDE5) is a major isoform of cGMP phosphodiesterase in a variety of human tumor cell lines and plays a key role in regulating intracellular cGMP concentrations ([cGMP]i). Here, we demonstrate that suppression of PDE5 gene expression by antisense pZeoSV2/ASP5 plasmid transfection results in a sustained increase in [cGMP]i, growth inhibition, and apoptosis in human colon tumor HT29 cells. With stable transfection, antisense transcripts exhibited a specific suppression in PDE5 activity, mRNA levels, and a 93 kDa hPDE5A1 protein. In cloned antisense cells, prolongation of the cell growth doubling times correlate positively with suppressed PDE5 activity and increased [cGMP]i. The growth inhibition in PDE5 antisense clones is due to an increased apoptotic rate and delayed cell-cycle progression. These results corroborate previous findings with the PDE5 inhibitor exisulind and its derivatives showing that sustained [cGMP]i induces apoptosis and growth inhibition in tumor cells. Furthermore, an inducible mitotic inhibitor p21WAF1/CIP1 has been found to account for the delay of cell-cycle progression in PDE5 antisense clones at G2/M phase. A proteolytic cleavage of p21WAF1/CIP1 in the antisense clones is also increased at the later stage of serum stimulation. The protein kinase G (PKG) inhibitor, KT5823, can prevent the cleavage of p21WAF1/CIP. These data substantiate a pivotal role for PDE5 as a modulator of apoptosis and cell-cycle progression for human carcinoma via a mechanism involving the activation of [cGMP]i/PKG signaling pathways. © 2004 Wiley-Liss, Inc. [source] Novel, cell-penetrating molecular transporters with flexible backbones and permanently charged side-chainsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2007N. Bodor Various cell-penetrating peptides have been discovered recently that can translocate across plasma membranes and can even carry large cargo molecules into the cells. Because under physiological conditions most of these peptides carry considerable positive charges due to the presence of basic amino acids such as arginine, we decided to investigate whether molecular transporters composed of permanently charged side-chains also possess such cell penetrating ability. Arginine-rich oligomers that have a backbone with increased flexibility due to incorporation of non-,-amino acids (,-aminocaproic acid) have been found to be effective molecular transporters. Here, we report the preparation of analogue structures by replacing the arginine residues with the quaternary form of a novel redox amino acid (Nys+) that contain a trigonelline moiety; it has already been shown possible to replace the original basic amino acid side-chain of neuropeptides without significant activity-loss due to the sufficiently close steric and electronic analogy between the new Nys+ and the original side-chains (in their protonated form, e.g., Arg+, Lys+). A nonamer analogue showed transporter activity resulting in increased cellular uptake in human carcinoma (HeLa) cells. [source] Homage to Theodor Boveri (1862,1915): Boveri's theory of cancer as a disease of the chromosomes, and the landscape of genomic imbalances in human carcinomas,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2009Thomas Ried First page of article [source] Jaw bone remodeling at the invasion front of gingival squamous cell carcinomasJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2003Masahiro Ito Abstract Background:, It is still unknown how jaw bone remodeling occurs at actual invasion sites of oral squamous cell carcinomas. Since there is no other human carcinomas which make a direct invasion of the bone, gingival carcinomas are valuable examples. Methods:, Twelve surgical specimens of gingival squamous cell carcinoma were examined histopathologically and immunohistochemically for remodeling of bone and its surrounding tissue. Results:, Three types of bone interfaces with carcinomatous invasion were distinguished. These included areas with bone resorption, smooth bone surface and new bone formation. In the bone-resorption area, numerous osteoclasts were located along the bone surface, which was surrounded by myxoid stroma. The myxoid stroma was characterized by immunopositivity for heparan sulfate proteoglycan (HSPG), abundant vascularity and macrophagic infiltration. In the bone-formation area, rows of osteoblasts were aligned on the bone surface. The stroma around osteoblasts was also HSPG-immunopositive, poor in vascularity but rich in activated fibroblasts. In the smooth-bone area, the stroma showed an organizing phase of granulation tissue with slender fibroblasts and mature collagen fibers but with less vascularity and inflammatory infiltrates. Conclusion:, The results indicate that the stromal architecture, especially in terms of its inflammatory cellular, vascular and matrix compositions, is strictly regulated in the timing and site of jaw bone remodeling which is causes by carcinomatous invasion. [source] DLC-1 suppresses non-small cell lung cancer growth and invasion by RhoGAP-dependent and independent mechanismsMOLECULAR CARCINOGENESIS, Issue 5 2008Kevin D. Healy Abstract Expression of the tumor suppressor deleted in liver cancer-1 (DLC-1) is lost in non-small cell lung (NSCLC) and other human carcinomas, and ectopic DLC-1 expression dramatically reduces proliferation and tumorigenicity. DLC-1 is a multi-domain protein that includes a Rho GTPase activating protein (RhoGAP) domain which has been hypothesized to be the basis of its tumor suppressive actions. To address the importance of the RhoGAP function of DLC-1 in tumor suppression, we performed biochemical and biological studies evaluating DLC-1 in NSCLC. Full-length DLC-1 exhibited strong GAP activity for RhoA as well as RhoB and RhoC, but only very limited activity for Cdc42 in vitro. In contrast, the isolated RhoGAP domain showed 5- to 20-fold enhanced activity for RhoA, RhoB, RhoC, and Cdc42. DLC-1 protein expression was absent in six of nine NSCLC cell lines. Restoration of DLC-1 expression in DLC-1-deficient NSCLC cell lines reduced RhoA activity, and experiments with a RhoA biosensor demonstrated that DLC-1 dramatically reduces RhoA activity at the leading edge of cellular protrusions. Furthermore, DLC-1 expression in NSCLC cell lines impaired both anchorage-dependent and -independent growth, as well as invasion in vitro. Surprisingly, we found that the anti-tumor activity of DLC-1 was due to both RhoGAP-dependent and -independent activities. Unlike the rat homologue p122RhoGAP, DLC-1 was not capable of activating the phospholipid hydrolysis activity of phospholipase C-,1. Combined, these studies provide information on the mechanism of DLC-1 function and regulation, and further support the role of DLC-1 tumor suppression in NSCLC. © 2007 Wiley-Liss, Inc. [source] Peroxisome proliferator-activated receptor gamma in human prostate carcinomaPATHOLOGY INTERNATIONAL, Issue 5 2009Yasuhiro Nakamura Peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear hormone receptor superfamily of transcription factors. Peroxisome proliferator-activated receptor gamma (PPAR,) plays an important role in the regulation of lipid homeostasis, adipogenesis, insulin resistance, and development of various organs. Agonists of PPAR, have been also reported to inhibit proliferation of prostate carcinoma cells as in other human malignancies, and these synthetic ligands have been used in differentiation-mediated therapy of various human carcinomas associated with high levels of PPAR,. The significance of PPAR, expression, however, was unknown in human prostate carcinoma tissues. The purpose of the present study was therefore to examine the immunolocalization of PPAR, in human prostate cancer tissues (40 cases) and correlate the findings with clinicopathological features of the patients in order to evaluate its possible biological significance. Twenty-nine patients were positive for PPAR, immunoreactivity (73%) and a significant inverse correlation was detected between PPAR, immunoreactivity, pT stage (P = 0.036), and serum concentration of prostate-specific antigen (P = 0.0004). In conclusion, PPAR, immunoreactivity is considered to be a new clinicopathological parameter of human prostate cancer. [source] Immunohistochemical comparison of ,-catenin expression by human normal epidermis and epidermal tumorsTHE JOURNAL OF DERMATOLOGY, Issue 11 2007Keiko FUKUMARU ABSTRACT ,-Catenin, a cytoplasmic protein that binds directly to the intracellular domain of cadherin, controls various functions such as cell adhesion. In many human carcinomas, E-cadherin-mediated cell,cell adhesion is lost or disturbed and related to metastasis. The purpose of this study was to compare the expression of ,-catenin in the normal epidermal keratinocytes and samples from cutaneous benign and malignant epidermal tumors in 140 patients. Our study population consisted of 140 patients with benign or malignant epidermal tumors. Using immunohistochemical methods, we compared the expression of ,-catenin in their normal epidermal keratinocytes, and in samples from 61 benign (seborrheic keratosis, n = 33; verruca vulgaris, n = 14; keratoacanthoma, n = 14), and 79 malignant (Bowen's disease, n = 18; basal cell carcinoma, n = 33; squamous cell carcinoma, n = 28) epidermal tumors. ,-Catenin was found to be expressed in the cell membrane of normal keratinocytes. Compared to other cell components of the normal epidermis, basal cells showed the strongest ,-catenin expression in all 140 patients. While absent in three of 61 benign tumors, compared to normal basal cells, the expression of ,-catenin in the other 58 tumors was not significantly different; it was reduced in 71 of 79 malignant tumors (P < 0.0001). In Bowen's disease, the expression of ,-catenin on the tumor cell membrane was reduced, however, strong expression was seen in the nuclei and cytoplasm. Our results suggest that ,-catenin expression on the membrane of keratinocytes is associated with the differentiation of normal keratinocytes but not with their stage of differentiation, nor with the proliferation ability of epidermal tumor cells. [source] Latent transforming growth factor binding protein 4 (LTBP-4) is downregulated in human mammary adenocarcinomas in vitro and in vivo,APMIS, Issue 6 2007SUSANNE MAUEL Transforming growth factor beta (TGF-ß) is able to inhibit proliferation of epithelial cells and is involved in the carcinogenesis of human mammary tumours. Three latent transforming growth factor-ß binding proteins (LTBP-1, -3 and -4) are involved in TGF-ß function. The aim of the study was to analyze the expression profiles of TGF-ß 1 and 2 and LTBP-4 in human mammary carcinoma cell lines as well as in human mammary tumours. Expression analysis was performed at the transcription and protein level under in vivo and in vitro conditions. LTBP-4 expression was quantitatively analysed in human carcinomas of the mammary gland and in healthy mammary tissues of the same patients. Downregulation of LTBP-4 in all investigated human mammary tumours compared to normal tissues could be demonstrated. Results also revealed that protein levels of TGF-ß 1 are downregulated and of TGF-ß 2 are upregulated in human mammary carcinoma cell lines compared to primary (normal) human mammary epithelial cells. LTBP-4 reduction in neoplasms leads to a possible decrease of TGF-ß 1 extracellular deposition with reduced TGF-ß 1 bioavailability. TGF-ß 2 was upregulated, which indicates a possible compensatory mechanism. This study demonstrated a possible functional role of LTBP-4 for TGF-ß bioavailability with respect to carcinogenesis of human mammary tumours in vivo and in vitro. [source] Mutational analysis of salvador gene in human carcinomasAPMIS, Issue 6 2003NAM JIN YOO It is believed that clonal expansion and cancer growth is the result of the deregulation of proliferation and cell death. Recently, salvador, a molecule that can regulate both cell proliferation and cell death, was identified. It was also reported that human salvador (hWW45) is mutated in some cancer cell lines. However, there have been no data regarding salvador gene mutations in human cancer tissues. To explore the hypothesis that the salvador gene might be similarly mutated in human cancer tissues, we analyzed the entire coding region of the salvador gene for the detection of somatic mutations in a series of human cancer tissues, including carcinomas from stomach, colon, liver and lung. However, using SSCP analysis, no mutation in the coding and splicing regions could be detected in the cancers. The data presented here suggest that salvador is not frequently mutated in human carcinoma tissues and that the mutation might be tumor-type specific. [source] Mutational analysis of Noxa gene in human cancersAPMIS, Issue 6 2003SUG HYUNG LEE There has been mounting evidence that dysregulation of apoptosis is involved in the mechanisms of cancer development and somatic mutations of apoptosis-related genes have been reported in human cancers. Noxa, a Bcl-2 homology 3 (BH3)-only member of the Bcl-2 family, is known to interact with anti-apoptotic Bcl-2 family members and induces apoptosis. The aim of this study was to explore the possibility that the Noxa gene is mutated in human cancers. We have analyzed the entire coding region and all splice sites of the Noxa gene for the detection of somatic mutations in a series of human cancers, including carcinomas from stomach, colon, liver, urinary bladder and lung by polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP), and DNA sequencing. We found one somatic mutation of the Noxa gene in a transitional cell carcinoma (TCC) of the urinary bladder. To evaluate the functional alterations of the mutant in apoptosis, we overexpressed the mutant and wild-type Noxa in 293T and HeLa cells, but could not find any significant difference in cell death between the wild-type and mutant Noxa. These data suggest that Noxa is rarely mutated in human carcinomas and that the contribution of Noxa gene mutation in the pathogenesis of human cancer might not be related to cell death mechanisms. [source] Immunohistochemical analysis of Smac/DIABLO expression in human carcinomas and sarcomas,APMIS, Issue 3 2003NAM JIN YOO Second mitochondria-derived activator of caspases (Smac/DIABLO) is released from mitochondria into the cytosol during apoptosis, promoting caspase activation by neutralizing the inhibition of inhibitor of apoptosis proteins (IAPs) on caspases. Alteration of apoptosis is essential for cancer development, and cancer cell death by radiation and chemotherapy is largely dependent upon apoptosis. In this study, archival tissues of 100 carcinomas and 50 sarcomas from various origins were analyzed by immunohistochemistry for the expression of Smac/DIABLO. Smac/DIABLO immunoreactivity was seen in 62 of 100 (62%) carcinomas, including 42 of 60 stomach carcinomas, 7 of 10 colorectal carcinomas, 4 of 10 lung carcinomas, 7 of 10 ovarian carcinomas, and 2 of 10 prostate carcinomas. Smac/DIABLO is expressed in 11 of 50 (22%) sarcomas, including 2 of 8 malignant schwannomas, 5 of 11 rhabdomyosarcomas, 2 of 7 malignant fibrous histiocytomas, 1 of 6 leiomyosarcomas, 0 of 8 angiosarcomas, 0 of 8 liposarcomas, and 1 of 2 Ewing's sarcomas. These data demonstrated that Smac/DIABLO expression levels vary depending on the individual cancer types. Furthermore, the present study showed that many human cancers do not express Smac/DIABLO, and suggest that lack of Smac/DIABLO expression in the cancer cells may inhibit apoptosis, thereby promoting their survival. [source] Human liver-specific organic anion transporter-2 is a potent prognostic factor for human breast carcinomaCANCER SCIENCE, Issue 10 2007Mitsuhisa Muto Human liver-specific organic anion transporter-2 (LST-2/OATP8/SLCO1B3) has been demonstrated to be expressed in various gastrointestinal carcinomas and also to play pivotal roles in the uptake of a wide variety of both endogenous and exogenous anionic compounds, including bile acids, conjugated steroids and hormones, into hepatocytes in the human liver. However, the biological significance of LST-2 in human carcinomas remains unknown. In the present study, we examined the expression of LST-2 in 102 cases of breast carcinoma using immunohistochemistry and correlated the findings with various clinicopathological parameters in order to examine the possible biological and clinical significance of LST-2. LST-2 immunoreactivity was detected in 51 cases (50.0%); of these 51 positive cases, LST-2 immunoreactivity was inversely correlated with tumor size (P = 0.0289). In addition, LST-2 immunoreactivity was significantly associated with a decreased risk of recurrence and improved prognosis by both univariate (P = 0.02 and P = 0.01) and multivariate (P = 0.03 and P = 0.01) analyses. In the estrogen receptor-positive groups, the LST-2-positive patients showed good prognoses. Considering that LST-2 transports estrone-3-sulfate, these results suggest that LST-2 overexpression is associated with a hormone-dependent growth mechanism of the breast cancer. The results of our present study demonstrate that LST-2 immunoreactivity is a potent prognostic factor in human breast cancer. (Cancer Sci 2007; 98: 1570,1576) [source] | |||||||||||||