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Ovarian cancer is the most lethal gynecologic malignancy and the five-year survival rate is only 35% after diagnosis. Epithelial ovarian cancer is a highly metastatic disease characterized by widespread peritoneal dissemination and ascites. The death incidences from ovarian cancer could be significantly lowered by developing new methods for the early diagnosis and treatment of this fatal disease. Several potential markers have been identified recently. However, mucins are the most promising markers for ovarian cancer diagnosis. Mucins are large extracellular, heavily glycosylated proteins and their aberrant expression has been implicated in the pathogenesis of a variety of cancers, including ovarian cancer. This review will summarize known facts about the pathological and molecular characteristics of ovarian cancer, the current status of ovarian cancer markers, as well as general information about mucins, the putative role of mucins in the progression of ovarian cancer and their potential use for the early diagnosis and treatment of this disease.
Ovarian Cancer
The life-time risk of having ovarian cancer is 1 in 70 women. This is the fifth leading cause of death for women in developing countries [1,2]. According to epidemiological studies, age is a common risk factor of ovarian cancer because the ovaries of post-menopausal women become smaller and folded. This folding results in deep cleft formations and formation of smaller cysts lined with ovarian surface epithelial (OSE) cells [3-6]. The other risk factors are: nulliparity, family history, history of fertility drug use and endocrine disorders. Multiparity, use of oral contraceptives, pregnancy and lactation all are associated with lower risk of ovarian cancer because of the decreased number of ovulation cycles [6-10]. Molecular alterations are also known to occur in ovarian cancer. These molecular alterations include mutation in the p53 gene which is known to be involved in DNA damage repair. Mutation in BRCA1 and BRCA2 has also been reported in ovarian tumors [11-15]. Inactivation or downregulation of tumor suppressor genes and amplification of oncogenes is also a potential cause of ovarian cancer. In ovarian tumors, the downregulation of OVCA1 and OVCA2 (tumor suppressor genes present in normal ovary) is reported, while their functions in normal ovary are not well known [11,16]. In contrast, overexpression/amplification of certain oncogenes like C-MYC, RAS, AKT, EGFR (ErbB1 or HER1), HER2/neu (ErbB2), CSF1 C-MYC, etc., is also well known in ovarian tumors [3-5,11,14,17-20].
Ovarian Cancer Staging and Histological Types
Phenotypically, the following types of epithelial ovarian cancers (90%) are classified based on their expressed properties related to the epithelium of the fallopian tube (serous tumors), proliferative endometrium (endometroid), endocervix or colonic epithelium (mucinous tumors), gestational endometrium (clear cell carcinoma), or the urinogenital tract (transitional or Brenner tumors) (Table 1). The remaining 10% of ovarian tumors are gonadal-stromal tumors (6%), germ cell tumors (3%) and metastatic tumors (1%) [5] (Table 1). The histological classification of ovarian tumors suggests four different stages in ovarian cancer: stage I (tumors involve one or both the ovaries, 5 year survival 60-90%), stage II (tumors involve one or both ovaries with pelvic extension, 5 year survival 37-66%), stage III (tumors involve one or both ovaries with intraperitoneal metastasis outside the pelvis, retroperitoneal nodes or both, 5 year survival 5-50%) and stage IV (tumors involve one or both ovaries with distant metastases, i.e. to lungs or liver, 5 year survival 0-17%) [5,21] (Table 2). The majority (90%) of ovarian cancers are epithelial ovarian carcinomas (EOC) which are thought to arise from the ovarian surface epithelium (OSE). OSE is the outermost mesothelial (peritoneal) lining and least component of the normal ovary, with no unique feature or known major functions. In addition, the early changes and minor anomalies remain undetected in this tissue [3,5,20]. Due to the anatomic location and the lack of early symptoms, it has become a difficult task to differentiate normal OSE, metaplasia, benign epithelial tumors and borderline tumors. Ovarian cancer can be treated effectively if detected at an early stage; but unfortunately, at the present time most of the ovarian tumors are not diagnosed before an advanced stage (stage III and IV) primarily due to the lack of reliable biomarkers of early diagnosis. Since most ovarian cancers are of epithelial nature and mucins are considered to be the hallmark of epithelial cells, the expression profile of mucins may serve as a potential diagnostic/prognostic and therapeutic target. In this article, we have compiled available information on the expression profile of different mucins in ovarian tumors and their potential role in ovarian cancer diagnosis and treatment.
Being that 90% of ovarian cancers are of epithelial origin, mucins may be attractive candidates for the detection of early stage ovarian cancer [1,2,5]. Mucins, large extracellular proteins, are heavily glycosylated with oligosaccharides and are generally known for providing protection to the epithelial tissues under normal physiological conditions [22-24]. Mucins are usually secreted by the epithelial tissues which remain in contact with relatively harsh environments such as airway epithelium, stomach epithelia, epithelial lining of intestine and ductal epithelial tissue of liver, pancreas, gall bladder, salivary gland, lachrymal gland, etc. In these tissues, epithelial cells are exposed to a variety of microorganisms, toxins, proteases, lipases, glycosidases and diverse microenvironment fluctuations that includes pH, ionic concentration, oxygenation, etc. [22-25]. All mucins share general characteristics. For example, they have repetitive domains of peptides rich in serine, threonine, and proline in their backbone. Serine and threonine are sites for O- and N-glycosylation. Presence of the tandem repeat domain which varies in number, length and O-glycosylation is the common structural feature of all mucins [23,26-29]. Their general structure and biochemical composition provides protection for the cell surface and specific molecular structures regulate the local microenvironment near the cell surface. In addition, mucins also communicate the information of the external environment to the epithelial cells via cellular signaling through membrane-anchored mucins [22-24,29]. It appears that mucins have the capability of serving as cell surface receptors and sensors and conducting signals in response to external stimuli for a variety of cellular responses like cell proliferation, cell growth, differentiation and apoptosis. These reports suggest that the aberrant expression of mucins may be implicated in the development and progression of ovarian cancer.
Type of Mucins
Currently, there are twenty known mucins which have been placed in two categories: secreted mucins (gel forming: MUC2 [30], MUC5AC [31], MUC5B [32], MUC6 [33], and non-gel forming: MUC7 [34] MUC8 [35] and MUC11[36]), and membrane bound mucins (MUC1[26], MUC3 [37], MUC4 [38], MUC9 [39], MUC10 [40], MUC12 [36], MUC13 [41], MUC16 [42,43], MUC17 [44], MUC18 [45] and MUC20 [46]).
Mucin Expression in Normal Ovary and Nonmalignant Ovarian Cell Lines
Goblet cells or glandular structures are not present in normal ovaries and, therefore, the normal ovarian tissues are not expected to express secretory mucins. Ovarian surface epithelium (OSE) expresses a mixed epithelo-mesenchymal phenotype and is the only compartment known to express mucins. MUC1 is the only well known mucin which is expressed by the OSE at a detectable level [3,4]. Cultured nonmalignant ovarian epithelial cell lines also express MUC1 (a membrane associated mucin) and MUC5AC (a secreted mucin) [47].
Mucin Expression in Ovarian Tumors
The expression of mucin genes by ovarian epithelial cells has not been studied in detail and only a few reports are available to address this issue. Phenotypically, EOCs are among the most variable tumors of any organ in that they may express ovarian tumor cells structurally related to the epithelium of different organs [4]. It has been shown that malignant ovarian tumors often express more mucins than benign and borderline ovarian tumors. Different studies (Table 3) on the expression of mucins in ovarian tumors have shown overexpression of MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC16 or CA125 [4,47-51]. In agreement with these studies, we also observed overexpression of MUC1, MUC4 and MUC16 in several ovarian tumors [52] with no or an undetectable level of MUC4 and MUC16 in normal ovarian tissues. In northern blot analysis a higher expression of MUC3 and MUC4 was reported in early stage ovarian tumor samples compared to the late stage ovarian tumor samples and it was proposed that they provided a protective function in ovarian cancer [47]. However, in our study we did not see this correlation with MUC4 [52]. The overexpression of MUC1 in various types and stages of ovarian tumor samples is reported in several studies [47,49,50]. Recently, our laboratory has identified aberrant expression of a novel membrane anchored mucin, MUC13, in ovarian cancer. In this study, MUC13 expression was undetectable in normal and benign ovarian samples while 66% of epithelial ovarian cancer samples showed a significantly higher MUC13 expression. MUC13 was predominantly localized on the apical membrane and in the cytoplasm. Moreover, MUC13 expression was significantly (p < 0.05) higher in mucinous and Brenners type of samples compared to other histological types of ovarian cancer samples and adjacent normal ovary samples [53]. The expression pattern of certain membrane bound mucins in ovarian tumors is shown in Figure 1.
Pathological Roles of Mucins in Ovarian Cancer
The acquirement of an invasive phenotype is one of the pivotal features of malignant ovarian cells. In order to progress and metastasize, ovarian cancer cells must lose cell contacts with neighboring cells, traverse the basement membrane and migrate through stroma to reach blood vessels or the lymphatic system. Mucins may be implicated in the exfoliation, dissemination and invasion of the ovarian cancer cells due to the highly glycosylated extracellular domain, which may protrude up to 200-2000 nm above the cell surface [54-56]. The overexpression of mucins can effectively interfere with the function of cell adhesion molecules by steric blocking of the interaction of the cell surface molecules. MUC1 is known to suppress cell aggression and cell adhesion properties by interfering with the functions of E-cadherin and other cell adhesion molecules in MUC1 overexpressing breast cancer cells [54-56]. In addition to this, mucins may also be involved in the invasion of the basement membrane by modulating cell-matrix attachment because of their diffused and basal localization in tumor cells. Mucins may also have an immunosuppressive effect by covering the surface of tumor cells and enabling access to the immune responsive cells [24,54-60]. The juxtamembrane domain of the membrane-bound mucins is known to promote cell proliferation by intercellular signaling mediated via one of their two/three EGF-like domains [24,55-61]. Moreover, the cytoplasmic tail of mucins like MUC1 is known to induce several cell signaling pathways, which promote the cell growth and proliferation in a variety of cancer cells [24,55-57,61-64]. Additionally, our recent study demonstrates that exogenous MUC13 expression induced morphological changes, including scattering of cells. These changes were abrogated through c-jun NH2-terminal kinase (JNK) chemical inhibitor (SP600125) or JNK2 siRNA. Moreover, a marked reduction in cell-cell adhesion and significant (p < 0.05) increases in cell motility, proliferation and tumorigenesis in a xenograft mouse model system were observed upon exogenous MUC13 expression. These cellular characteristics were correlated with up-regulation of HER2, p21-activated kinase1 (PAK1) and p38 protein expression [53]. Additionally, recent studies have shown the role of MUC16/CA125 in ovarian cancer metastasis. MUC16 mucin interacts with the glycosylphosphatidylinositol anchored glycoprotein mesothelin at high affinity and facilitates the peritoneal metastasis of ovarian cancer cells [65,66]. Moreover, MUC16/CA125 expression has been shown to inhibit the cytotoxic responses of human natural killer (NK) cells and downregulate CD16 activity in ovarian cancer cells. It has also been shown that MUC16/CA125 selectively binds to 30-40% of CD16+ NK cells in EOC patients. These studies suggest immunosuppressive properties of MUC16/CA125 [67]. These above mentioned findings demonstrate the aberrant expression of mucins in ovarian cancer and show that mucin expression may alter the cellular characteristics of ovarian cancer cells and also imply a significant role of mucins in the pathogenesis of ovarian cancer.
Mucins as Serum Marker of Ovarian Cancer
The structural characteristics of mucins suggest the presence of potential proteolytic cleavage sites in most mucin genes and several are known to cleave at the cell surface. Mucins, which are normally confined to the epithelial surfaces, become exposed to circulation and their overexpression may establish their potential as a tumor marker and/or diseased condition. Mucins already have shown their great potential as serum markers of ovarian and various other tumors. Aberrant O-glycosylation of mucins is particularly prominent in epithelial cancers. This feature has been termed "glycodynamics". These heterogeneously O-glycosylated mucins aberrantly enter the bloodstream in malignant conditions which provide diagnostic biomarkers for detection and monitoring of cancer. Although mucins are rapidly degraded by glycan-recognizing hepatic clearance receptors in the liver, small subsets of carcinoma mucins remained unrecognized by clearance systems. Thus, circulating cancer mucins used as clinical diagnostic markers likely represent only the clearance-resistant "tip of the iceberg" [68]. For example, O-glycans on circulating MUC16 recognized by antibody CA125 provide for diagnosis and monitoring of ovarian cancers [42]. CA125, an established serum marker of ovarian tumors, has been recently identified as a member of a mucin family and named MUC16 [42,43,69]. MUC16 is a large, heavily glycosylated transmembrane mucin. Several studies have shown the importance of CA125/MUC16 in ovarian cancer diagnosis. In fact, an elevated level of CA125/MUC16 is a gold standard non-invasive test for ovarian cancer diagnosis [70,71]. A decrease in CA125 can provide a surrogate marker to determine the response to chemotherapeutic drug(s) during the treatment procedure [72]. Moreover, antigens such as CA19-9, CA50, and CA242 are also the serum markers of various malignant conditions and are present on heavily glycosylated, high molecular weight mucins [22,73,74]. In breast cancers, serum MUC1 measured by CA15-3 is a well established assay and has been shown to correlate with the clinical course [75]. MUC1 and MUC4 are also known to be overexpressed in ovarian tumors. Despite having a great importance in ovarian cancer, CA125 does not display an elevated serum level in over 50% of the women with early stage tumors because this antigen is not expressed in most early stage ovarian tumors [1,76-79]. Additionally, an elevated level of CA125 was observed in some other (pancreatic, breast, liver, bladder and lung) cancers, benign conditions (diverticulitis, uterine fibroids, endometriosis, and ectopic pregnancy) and physiological conditions (pregnancy and menstruation). Therefore, the discovery of new serum tumor markers capable of complementing CA125 may allow for the development of a reliable test for the early stage diagnosis of ovarian cancer. Our recent and some previous studies showed the overexpression of MUC4 in a majority of early stage ovarian tumors and a combined panel of MUC1, MUC4 and MUC16 dramatically increased the sensitivity of MUC16 staining test [52]. Additionally, a recent study suggests the overexpression of MUC4 in ovarian carcinoma cells present in peritoneal effusions [80]. Furthermore, our laboratory has recently identified the aberrant expression of a novel transmembrane mucin, MUC13, in ovarian tumor samples compared to normal/benign ovarian tissue samples [53]. Like other membrane-associated mucins, MUC4 and MUC13 also have a proteolytic cleavage site in its structure which may allow the cleavage of the extracellular part of MUC4 and MUC13 and their release in the blood stream [29]. A similar process occurs in case of MUC1 and MUC16. These data suggest that a combined panel of different mucins may improve sensitivity and accuracy of the currently used serum based diagnosis of ovarian cancer. Further, aberrant mucin expression may be immunogenic and may elicit a potent antibody response. This antibody response may also serve as a disease indicator. A recent study demonstrated the presence of MUC1 antibodies in blood plasma samples which was inversely correlated with risk of ovarian cancer [81]. These studies suggest that the aberrant expression of mucins holds great promise to serve as a surrogate marker of ovarian cancer and ovarian cancer prognosis.
Use of Mucins in Radioimmunodiagnosis (RID) and Radioimmunotherapy (RIT)
Monoclonal antibodies against mucins may have potential applications in improving the diagnosis and therapy of ovarian tumors, although very few published studies are available to address this issue, so far, and continued investigations are certainly required. The much higher expression of mucins (MUC1, MUC4, MUC5AC, MUC13 and MUC16) in ovarian tumors compared to the surrounding normal tissues can be exploited for the purpose of radioimmunodiagnosis (RID) and radioimmunotherapy (RIT). MUC1 monoclonal antibodies radiolabeled with γ-emitting radioisotopes like 99mTC and 111In have been successfully used for the radioimmunodiagnosis of various malignancies [82]. As an extension of this technique, monoclonal antibodies to the mucins, radiolabeled with β-emitting isotopes such as 67Cu, or 188Re, may be employed for the irradiation of spreading tumor cells (radioimmunotherapy) while sparing normal cells [82-84]. At present, MUC1 and MUC16 are the best and only characterized mucins and monoclonal antibodies against MUC1 and MUC16 are under preclinical and clinical investigations for ovarian cancer treatment (Table 4). Therapeutic efficacy of anti-MUC1 MAb (HMFG1: anti-human milk fat globules) radiolabeled with 90Y, 186Re and 131I was investigated in an OVCAR3 ovarian cancer xenograft model. These radiopharmaceuticals significantly improved survival in treated mice compared to control mice. Similarly, radiolabeled MUC16 MAbs also caused significant delay in animal death. MUC13 is another potential mucin which is highly expressed on the surface of ovarian cancer cells, indicating its potential as a target for RID and RIT. An emerging concept in radioimmunotherapy is nano-radioimmunotherapy (Nano-RIT). In these studies radiolabeled antibodies are coupled with drug loaded liposomes or nanoparticles. This approach will overcome some of the major obstacles associated with conventional strategies and will improve tumor uptake and retention time of radioimmunoconjugates [85,86]. The radioimmunoconjugates can be safely administered via an intravenous route despite the fact they are mouse monoclonal antibodies and capable of inducing human anti-mouse antibody (HAMA) responses. However, this problem can be minimized in the future by using modern antibody engineering techniques [87].
Anti-Cancer Vaccines Based on Mucins
In recent years, projects associated with the development of tumor vaccines have received considerable attention (Table 4). A further possible approach involves the use of mucins as a vaccine and target for immune responses (Table 4) [88,89]. Three types of strategies can be employed for vaccine development: antibody-based, antigen-based and cell-based. As we mentioned earlier, certain membrane anchored mucins which are over/aberrantly expressed in ovarian cancer can be targeted for monoclonal antibody generation and anti-cancer vaccine development. Antibody generated against a tumor antigen can trigger potent antibody-dependent cellular cytotoxicity and T-cell response. Additionally, monoclonal antibodies can persuade anti-idiotypic antibodies that mimic the epitopes in tumor antigens and can elicit a potent anti-cancer response in patients. For an anti-cancer vaccine, synthetic peptide or DNA that encodes for a tumor antigen can be administered to the patient and over time the patient will develop an immune response by activation of cytotoxic T cells. In a cell-based vaccine approach, tumor cells of the same patient (autologous) or a different patient (allogeneic) or dendritic cells (activated by cancer antigen) are administered to the cancer patient to stimulate the immune system. The induction of potential anti-MUC responses may provide potential benefits in targeting tumors overexpressing mucin antigens. MUC1 has been successfully used as a target for immuno-directed therapies and as a marker of disease progression [88-90]. The efficacy of the immune response to mucins or mucin peptides can be effectively augmented by conjugation of immune adjuvant and/or carrier proteins like Bacille Calmette-Guerin (BCG) and keyhole limpet hemocyanin (KLH). A cognate of the MUC1 peptide conjugated with KLH and Quillaja saponaria (QS-21) has entered into clinical trials for prostate cancer [91,92]. The use of naked DNA is another attractive and relatively simple approach for vaccination studies. MUC1 cDNA has been used as a cancer vaccine in mouse models and has been shown to result in long-term growth suppression of tumors [93,94]. Additionally, dendritic cells pulsed with mucin derived peptides were able to induce a potent cytotoxic T-cell response and provide therapeutic benefits [95,96]. For ovarian tumors, which are known to overexpress mucins, this may be a potential treatment approach with a better survival outcome.
The mucin gene family has considerable potential importance in the cell biology, diagnosis and treatment of ovarian malignancies. Various studies have shown the overexpression of MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC16 in a variety of ovarian tumors. In particular, a combined panel of MUC4, MUC5AC, and MUC16 may offer an effective and reliable diagnostic system and target for the management of various histological grades and types of ovarian cancer, although their biological functions are not clearly defined. The development of new molecular biology techniques will allow researchers to determine the biological role of mucins in the process of ovarian tumor progression and response to therapy. The gene locus of the majority of mucin genes has been identified and, therefore, may be a potential target for future gene-based therapies, including immunoliposome targeted techniques. The use of mucins as targets for radioimmunodiagnosis and radioimmunotherapy is also being explored and appears to be a potential approach for the diagnosis and treatment of ovarian tumors which overexpress mucins. The advancement in the area of antibody engineering techniques provides an opportunity to produce single-chain, divalent, tetravalent and humanized antibody constructs from murine monoclonal antibodies. These molecules will be significantly less immunogenic to the human host than their intact mouse Ig counterparts, and may allow repeated intravenous/intraperitoneal administrations of targeting radioconjugated molecules, improved tumor tissue penetration due to reduced physical size with a minimal or no risk of an HAMA response. In the light of available information, we conclude that switching of mucin genes occurs in ovarian cancer, which can be utilized for the early diagnosis and treatment of ovarian tumors.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
SCC drafted the manuscript. DK and MJ participated in substantial contribution to revising of the manuscript. All authors read and approved the final manuscript.
This work was supported by a Sanford Research/USD grant and Department of Defense Grants (PC073887) awarded to SCC and (PC073643) awarded to MJ. DK is supported by SC1 (CA141935) and U56 (CA101563) grants from NCI. We thank Cathy Christopherson for editorial assistance with the manuscript.
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Hanski C, Hofmeier M, Schmitt-Graff A, Riede E, Hanski ML, Borchard F, Sieber E, Niedobitek F, Foss HD, Stein H, Riecken EO: Overexpression or ectopic expression of MUC2 is the common property of mucinous carcinomas of the colon, pancreas, breast, and ovary.
J Pathol 1997, 182:385-391. PubMed Abstract | Publisher Full Text
Chauhan SC, Singh AP, Ruiz F, Johansson SL, Jain M, Smith LM, Moniaux N, Batra SK: Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125).
Mod Pathol 2006, 19:1386-1394. PubMed Abstract | Publisher Full Text
Chauhan SC, Vannatta K, Ebeling MC, Vinayek N, Watanabe A, Pandey KK, Bell MC, Koch MD, Aburatani H, Lio Y, Jaggi M: Expression and functions of transmembrane mucin MUC13 in ovarian cancer.
Cancer Res 2009, 69:765-774. PubMed Abstract | Publisher Full Text
Kondo K, Kohno N, Yokoyama A, Hiwada K: Decreased MUC1 expression induces E-cadherin-mediated cell adhesion of breast cancer cell lines.
Cancer Res 1998, 58:2014-2019. PubMed Abstract | Publisher Full Text
Wesseling J, Valk SW, Hilkens J: A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/MUC1.
Mol Biol Cell 1996, 7:565-577. PubMed Abstract | PubMed Central Full Text
Wesseling J, Valk SW, Vos HL, Sonnenberg A, Hilkens J: Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components.
J Cell Biol 1995, 129:255-265. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Kohlgraf KG, Gawron AJ, Higashi M, Meza JL, Burdick MD, Kitajima S, Kelly DL, Caffrey TC, Hollingsworth MA: Contribution of the MUC1 tandem repeat and cytoplasmic tail to invasive and metastatic properties of a pancreatic cancer cell line.
Cancer Res 2003, 63:5011-5020. PubMed Abstract | Publisher Full Text
Komatsu M, Carraway CA, Fregien NL, Carraway KL: Reversible disruption of cell-matrix and cell-cell interactions by overexpression of sialomucin complex.
J Biol Chem 1997, 272:33245-33254. PubMed Abstract | Publisher Full Text
Komatsu M, Tatum L, Altman NH, Carothers Carraway CA, Carraway KL: Potentiation of metastasis by cell surface sialomucin complex (rat MUC4), a multifunctional anti-adhesive glycoprotein.
Int J Cancer 2000, 87:480-486. PubMed Abstract | Publisher Full Text
Komatsu M, Yee L, Carraway KL: Overexpression of sialomucin complex, a rat homologue of MUC4, inhibits tumor killing by lymphokine-activated killer cells.
Cancer Res 1999, 59:2229-2236. PubMed Abstract | Publisher Full Text
Kashiwagi H, Kijima H, Dowaki S, Ohtani Y, Tobita K, Yamazaki H, Nakamura M, Ueyama Y, Tanaka M, Inokuchi S, Makuuchi H: MUC1 and MUC2 expression in human gallbladder carcinoma: a clinicopathological study and relationship with prognosis.
Oncol Rep 2001, 8:485-489. PubMed Abstract
Li Y, Kufe D: The Human DF3/MUC1 carcinoma-associated antigen signals nuclear localization of the catenin p120(ctn).
Biochem Biophys Res Commun 2001, 281:440-443. PubMed Abstract | Publisher Full Text
Li Y, Kuwahara H, Ren J, Wen G, Kufe D: The c-Src tyrosine kinase regulates signaling of the human DF3/MUC1 carcinoma-associated antigen with GSK3 beta and beta-catenin.
J Biol Chem 2001, 276:6061-6064. PubMed Abstract | Publisher Full Text
Li Y, Ren J, Yu W, Li Q, Kuwahara H, Yin L, Carraway KL, Kufe D: The epidermal growth factor receptor regulates interaction of the human DF3/MUC1 carcinoma antigen with c-Src and beta-catenin.
J Biol Chem 2001, 276:35239-35242. PubMed Abstract | Publisher Full Text
Rump A, Morikawa Y, Tanaka M, Minami S, Umesaki N, Takeuchi M, Miyajima A: Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion.
J Biol Chem 2004, 279:9190-9198. PubMed Abstract | Publisher Full Text
Gubbels JA, Belisle J, Onda M, Rancourt C, Migneault M, Ho M, Bera TK, Connor J, Sathyanarayana BK, Lee B, Pastan I, Patankar M: Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors.
Mol Cancer 2006, 5:50. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
Belisle JA, Gubbels JA, Raphael CA, Migneault M, Rancourt C, Connor JP, Patankar MS: Peritoneal natural killer cells from epithelial ovarian cancer patients show an altered phenotype and bind to the tumour marker MUC16 (CA125).
Immunology 2007, 122:418-429. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Wahrenbrock MG, Varki A: Multiple hepatic receptors cooperate to eliminate secretory mucins aberrantly entering the bloodstream: are circulating cancer mucins the "tip of the iceberg"?
Cancer Res 2006, 66:2433-2441. PubMed Abstract | Publisher Full Text
Bast RC Jr, Xu FJ, Yu YH, Barnhill S, Zhang Z, Mills GB: CA 125: the past and the future.
Int J Biol Markers 1998, 13:179-187. PubMed Abstract
Bast RC Jr, Klug TL, St John E, Jenison E, Niloff JM, Lazarus H, Berkowitz RS, Leavitt T, Griffiths CT, Parker L, Zurawski V Jr, Knapp R: A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer.
N Engl J Med 1983, 309:883-887. PubMed Abstract | Publisher Full Text
Bast RC Jr, Badgwell D, Lu Z, Marquez R, Rosen D, Liu J, Baggerly KA, Atkinson EN, Skates S, Zhang Z, Lokshin A, Menon U, Jacobs I, Lu Kl: New tumor markers: CA125 and beyond.
Int J Gynecol Cancer 2005, 15(Suppl 3):274-281. PubMed Abstract | Publisher Full Text
Rustin GJ, Bast RC Jr, Kelloff GJ, Barrett JC, Carter SK, Nisen PD, Sigman CC, Parkinson DR, Ruddon RW: Use of CA-125 in clinical trial evaluation of new therapeutic drugs for ovarian cancer.
Clin Cancer Res 2004, 10:3919-3926. PubMed Abstract | Publisher Full Text
Kim YS, Gum J Jr, Brockhausen I: Mucin glycoproteins in neoplasia.
Glycoconj J 1996, 13:693-707. PubMed Abstract | Publisher Full Text
Kim YS, Gum JR Jr, Crawley SC, Deng G, Ho JJ: Mucin gene and antigen expression in biliopancreatic carcinogenesis.
Ann Oncol 1999, 10(Suppl 4):51-55. PubMed Abstract | Publisher Full Text
Robertson JF, Jaeger W, Syzmendera JJ, Selby C, Coleman R, Howell A, Winstanley J, Jonssen PE, Bombardieri E, Sainsbury JR, Gronberg H, Kumpulainen E, Blamey RW: The objective measurement of remission and progression in metastatic breast cancer by use of serum tumour markers. European Group for Serum Tumour Markers in Breast Cancer.
Eur J Cancer 1999, 35:47-53. PubMed Abstract | Publisher Full Text
Fritsche HA, Bast RC: CA 125 in ovarian cancer: advances and controversy.
Clin Chem 1998, 44:1379-1380. PubMed Abstract | Publisher Full Text
Jacobs I, Bast RC Jr: The CA 125 tumour-associated antigen: a review of the literature.
Hum Reprod 1989, 4:1-12. PubMed Abstract | Publisher Full Text
Jacobs IJ, Oram DH, Bast RC Jr: Strategies for improving the specificity of screening for ovarian cancer with tumor-associated antigens CA 125, CA 15-3, and TAG 72.3.
Obstet Gynecol 1992, 80:396-399. PubMed Abstract
Jacobs IJ, Rivera H, Oram DH, Bast RC Jr: Differential diagnosis of ovarian cancer with tumour markers CA 125, CA 15-3 and TAG 72.3.
Br J Obstet Gynaecol 1993, 100:1120-1124. PubMed Abstract
Davidson B, Baekelandt M, Shih Ie M: MUC4 is upregulated in ovarian carcinoma effusions and differentiates carcinoma cells from mesothelial cells.
Diagn Cytopathol 2007, 35:756-760. PubMed Abstract | Publisher Full Text
Cramer DW, Titus-Ernstoff L, McKolanis JR, Welch WR, Vitonis AF, Berkowitz RS, Finn OJ: Conditions associated with antibodies against the tumor-associated antigen MUC1 and their relationship to risk for ovarian cancer.
Cancer Epidemiol Biomarkers Prev 2005, 14:1125-1131. PubMed Abstract | Publisher Full Text
Hughes OD, Perkins AC, Frier M, Wastie ML, Denton G, Price MR, Denley H, Bishop MC: Imaging for staging bladder cancer: a clinical study of intravenous 111indium-labelled anti-MUC1 mucin monoclonal antibody C595.
BJU Int 2001, 87:39-46. PubMed Abstract | Publisher Full Text
Hughes OD, Bishop MC, Perkins AC, Frier M, Price MR, Denton G, Smith A, Rutherford R, Schubiger PA: Preclinical evaluation of copper-67 labelled anti-MUC1 mucin antibody C595 for therapeutic use in bladder cancer.
Eur J Nucl Med 1997, 24:439-443. PubMed Abstract | Publisher Full Text
Hughes OD, Bishop MC, Perkins AC, Wastie ML, Denton G, Price MR, Frier M, Denley H, Rutherford R, Schubiger PA: Targeting superficial bladder cancer by the intravesical administration of copper-67-labeled anti-MUC1 mucin monoclonal antibody C595.
J Clin Oncol 2000, 18:363-370. PubMed Abstract | Publisher Full Text
McQuarrie S, Mercer J, Syme A, Suresh M, Miller G: Preliminary results of nanopharmaceuticals used in the radioimmunotherapy of ovarian cancer.
J Pharm Pharm Sci 2005, 7:29-34. PubMed Abstract | Publisher Full Text
Cirstoiu-Hapca A, Buchegger F, Bossy L, Kosinski M, Gurny R, Delie F: Nanomedicines for active targeting: Physico-chemical characterization of paclitaxel-loaded anti-HER2 immunonanoparticles and in vitro functional studies on target cells.
Eur J Pharm Sci 2009, 38(3):230-7. PubMed Abstract | Publisher Full Text
Batra SK, Jain M, Wittel UA, Chauhan SC, Colcher D: Pharmacokinetics and biodistribution of genetically engineered antibodies.
Curr Opin Biotechnol 2002, 13:603-608. PubMed Abstract | Publisher Full Text
Graham RA, Burchell JM, Taylor-Papadimitriou J: The polymorphic epithelial mucin: potential as an immunogen for a cancer vaccine.
Cancer Immunol Immunother 1996, 42:71-80. PubMed Abstract | Publisher Full Text
Syrigos KN, Karayiannakis AJ, Zbar A: Mucins as immunogenic targets in cancer.
Anticancer Res 1999, 19:5239-5244. PubMed Abstract
Brossart P, Heinrich KS, Stuhler G, Behnke L, Reichardt VL, Stevanovic S, Muhm A, Rammensee HG, Kanz L, Brugger W: Identification of HLA-A2-restricted T-cell epitopes derived from the MUC1 tumor antigen for broadly applicable vaccine therapies.
Blood 1999, 93:4309-4317. PubMed Abstract | Publisher Full Text
Goydos JS, Elder E, Whiteside TL, Finn OJ, Lotze MT: A phase I trial of a synthetic mucin peptide vaccine. Induction of specific immune reactivity in patients with adenocarcinoma.
J Surg Res 1996, 63:298-304. PubMed Abstract | Publisher Full Text
Reddish MA, MacLean GD, Poppema S, Berg A, Longenecker BM: Pre-immunotherapy serum CA27.29 (MUC-1) mucin level and CD69+ lymphocytes correlate with effects of Theratope sialyl-Tn-KLH cancer vaccine in active specific immunotherapy.
Cancer Immunol Immunother 1996, 42:303-309. PubMed Abstract | Publisher Full Text
Graham RA, Burchell JM, Beverley P, Taylor-Papadimitriou J: Intramuscular immunisation with MUC1 cDNA can protect C57 mice challenged with MUC1-expressing syngeneic mouse tumour cells.
Int J Cancer 1996, 65:664-670. PubMed Abstract | Publisher Full Text
Johnen H, Kulbe H, Pecher G: Long-term tumor growth suppression in mice immunized with naked DNA of the human tumor antigen mucin (MUC1).
Cancer Immunol Immunother 2001, 50:356-360. PubMed Abstract | Publisher Full Text
Lepisto AJ, Moser AJ, Zeh H, Lee K, Bartlett D, McKolanis JR, Geller BA, Schmotzer A, Potter DP, Whiteside T, Finn OJ, Ramanathan RK: A phase I/II study of a MUC1 peptide pulsed autologous dendritic cell vaccine as adjuvant therapy in patients with resected pancreatic and biliary tumors.
Cancer Ther 2008, 6:955-964. PubMed Abstract | PubMed Central Full Text
Wierecky J, Mueller M, Brossart P: Dendritic cell-based cancer immunotherapy targeting MUC-1.
Cancer Immunol Immunother 2006, 55:63-67. PubMed Abstract | Publisher Full Text
Heinzelmann-Schwarz VA, Gardiner-Garden M, Henshall SM, Scurry JP, Scolyer RA, Smith AN, Bali A, Bergh P, Baron-Hay S, Scott C, Fink D, Hacker NF, Sutherland RL, O'Brien PM: A distinct molecular profile associated with mucinous epithelial ovarian cancer.
Br J Cancer 2006, 94:904-913. PubMed Abstract | Publisher Full Text | PubMed Central Full Text


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Target plans to cut thousands of jobs in corporate restructure
Target Corp. plans to eliminate "several thousand positions," primarily at its Minneapolis headquarters, as part of a two-year corporate restructuring.
Target Corp. plans to eliminate "several thousand positions," primarily at its Minneapolis headquarters, as part of a two-year corporate restructuring.
Union negotiators for 3,500 Twin Cities area hospital workers say they're reached a tentative contract agreement covering eight medical centers.
The nation's largest electronics chain raised its quarterly dividend 21 percent and plans to give shareholders an additional one-time payment after reporting a better-than-expected fourth-quarter profit.
It's largely symbolic, since the city doesn't invest in fossil fuel firms. But a committee hearing on the matter drew many residents and students in support.
Mayo Clinic is working with a concierge service to bring more Chinese patients to Rochester. It's also planning a new venture to serve health providers in China.
MHS History Forum with historian Ernest Freeberg, author of "The Age of Edison: Electric Light and the Invention of Modern America." How the lightbulb changed nearly everything in American life and society.
The luxury lodging will include an indoor connection to the airport, hotel entrepreneur Jim Graves said Monday. The full airport commission is expected to approve the deal March 17.
Boston Scientific is buying American Medical Systems' men's and prostate health business, which has 275 Minnesota employees.
Declining passenger numbers are leading Allegiant to end scheduled flights from Duluth to Las Vegas. The service, which began in 2006, will end Aug. 18, airport officials said.
A bill introduced in the Minnesota House would lift a sticking point between the two states that remains after a series of reconciliation attempts.
Just five years ago, the Nasdaq composite index hovered around the 2,300 mark.
From the Intelligence Squared series. Are America's best days behind us? Four experts debate the motion, "Declinists be damned: bet on America."
Amy Lindgren joins MPR News with Kerri Miller every other month for advice about jobs and careers.
If Wisconsin's bill passes through the state assembly, it will become the 25th state to have such legislation.
A new report suggests economic growth is ahead for nine Midwestern and Plains states, including Minnesota.
The Metropolitan Council opened the Section 8 waiting list earlier this week for the first time in eight years.
The park board will go along with plans for a train bridge crossing the channel between Cedar Lake and Lake of the Isles. The project still faces another legal hurdle.
Comcast disputed the city's allegations but agreed to the settlement as part of a larger deal that lets it provide cable TV service in St. Paul for another 10 years.
Telecom giant Comcast is accusing competitor CenturyLink of trying to skirt state law in its bid to provide cable TV service in Minneapolis.
St. Jude Medical expects to pay about $14.5 million to settle litigation over Riata-brand wires that connect a defibrillator to the heart. The discontinued product is linked to 22 deaths.

subset: commoncrawl


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Donate to NOLS
Contact Us
Inspired Life: NOLS Grad Nico Marceca Is Giving Back in More Ways Than One
By Collin McRann, NOLS Alumni Intern
For many NOLS grads, their course is the beginning of a fresh perspective that finds its limits far beyond backcountry survival and wilderness ethics. Many students have discovered that leadership experience in the wilderness creates a unique sense of awareness about the environment and ones self that ultimately helps them throughout their lives. Such is the case with Nico Marceca, a 2005 NOLS Alaska Backpacking and Sea Kayaking graduate who found not only inspiration and companionship during his course, but a new direction in life.
Before Nico was 12, his younger sister, Siena, and father became terminally ill. Siena had been struggling with a degenerative brain disorder since birth, while his father was stricken with pancreatic cancer. They both fought to hold on, but by 2001 had passed away within months of each other. This very large and sudden void in Nico's life left him hurt and looking for answers, but through the pain he never forgot what his sister had represented in his eyes. "She taught me many lessons and instilled in me much appreciation for the delicate life of this world," he said.
So, in the summer of 2005, Nico headed for Alaska to spend a month in the wilderness with NOLS. It would be full of hardships, as well as good times, but it was something that he would never forget. "NOLS really changed my life, it opened my eyes toward the world, taught me to be a leader and made me realize that one person can make a difference," he said. The course took him through some of Alaska's most remote and scenic terrain, but that only characterized part of the experience. "Every night we would sit around with hot drinks and just talk about a life of simplicity, about appreciating the life you have and the people around you," he said.
As with almost any expedition into the wilderness, much of the atmosphere is defined by the people you're with. "The interactions with other college-age students who have advocated for change was definitely part of how I was able to redirect my life and my way of thinking," said Nico. The simplicity of being in a faraway and different place with time that allowed for personal reflection helped him decide what he wanted to do and where to go next.
Once his course came to end, Nico was determined to take his inspiration and do something with it to honor the family members he had lost. Before Nico's father died, he started a handful of charities around the world in honor of his daughter Siena, so Nico decided on the Siena Home in Eluru, India as his new cause. Siena Home is a shelter that provides food and medical support to impoverished and abandoned children and aims to teach them practical living and working skills so one day they may improve their lives and escape their poverty-stricken situations. Even though it is a relatively new organization, Siena Home has been extremely successful, growing to house over 160 children and continuing to expand due to its spreading word-of-mouth reputation. "Siena Home has grown a lot, it is supported entirely by donations, and at one point poor children from all around the area started to just walk to it, picking more children up along the way, and by the time they got there it was a massive group," said Nico.
How Nico intends to help Siena Home, and perhaps other charities in the future, makes his situation even more unique because it also encourages a strong environmental ethic. His plans involve Citizenre, a company that specializes in affordable solar energy through the mass production and distribution of solar energy systems to the average home. Nico has signed on with Citizenre as a promoter and receives money for every person he signs up for the program; but, unlike most employees working on commission, Nico intends to give his initial profits to Siena Home. "Right now the home needs a new bore well and rain water collector; the total cost is around $10,000. Through Citizenre, I'm confident I can raise the money because for every person I sign up, I receive $150. Just sixty-seven people would be enough to raise the money for Siena Home, but my goal is to reach over 1,000, and I hope the NOLS community will be interested," he said.
Citizenre aims to have over 25 percent of the US population on solar power by the year 2025 and works on a system of renting equipment to individuals. To keep their costs down, they plan to manufacture their own systems rather than buy them from a third-party source. Nico is hopeful this system will be successful, and has already been able to sign up five people, with all the commission going to Siena Home.
The final kicker in all this do-gooding? Nico just recently graduated from high school and has signed up for a second NOLS course, a Semester in Baja. Knowing that he was able to take away so much from his first course, it is safe to say that inspiration and purpose shall meet once again.
If you're not getting The Leader in the mail and you want to, click here.
Request a Catalog or call 1-800-710-6657 NOLS, 284 Lincoln Street, Lander, WY 82520-2848, USA Copyright © 2015 National Outdoor Leadership School. All rights reserved. NOLS is a 501(c)3 nonprofit educational institution.


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Phalaenopsis Orchid Heart Plant
She is forever and always your sweetie. Let her know how much she is loved with this exquisite plant. Lush ivy is masterfully formed into a heart that surrounds a striking white Phalaenopsis orchid plant. More
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Becoming a member of satic is important to you and to SA tourism
Membership sign up
SATIC engages, represents, strengthens & empowers the South Australian tourism industry.
About SATIC
SATIC actively lobbies on behalf of its members to achieve the best business environment for tourism operators in this State. We are your voice. Latest post: SA Tourism Commission Board to be replaced
Read more2015 SATIC Tourism Conference
SAVE THE DATE for the 2015 SATIC Tourism Conference to be held on Wednesday, 27 May. The full program will be available late March.
Read moreUpcoming training & events calendar
04 Mar 2015
Marketing on Tight Budgets Workshop
10 Apr 2015
2014 Australian Tourism Awards Gala Dinner - Adelaide
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6 Steps to Doing Your Kids' Trust Fund Right
By Rick Kahler
AdviceIQ) -- How do you stop your offspring squandering their inheritance? When passing wealth to your kids, consider creating a trust to limit the later generation's ability to tap into the principal.
Several astute readers suggested this strategy after my recent article cited research that shows 90% of inherited wealth is gone by the third generation.
There is no question a trust, done correctly, can go a long way to preserve wealth after the death of the wealth accumulator. Let's explore what "done correctly" means.
1. Trust law is complex. Engage an accountant and attorney with strong skills and expertise in trusts.
2. Be sure the assets you intend to go into the trust will actually transfer. Retirement plans such as individual retirement accounts, 401(k)'s and profit-sharing plans will pass to whomever you listed as the beneficiary. This must be the trust. In addition, the trust must include a number of special provisions for a retirement plan to be distributed according to your wishes and not as a fully taxable lump sum. Annuities, insurance policies and accounts with a transfer-on-death clause will also pass to the named beneficiary. Assets held in joint tenancy will not. Many married couples jointly own most of their major assets, such as the family home, investment real estate, brokerage accounts or bank accounts. 3. Be sure there are enough assets in the trust to justify the trustee fees. Most professional corporate trustees charge $3,500 to $10,000 annually, or up to 1% of the trust assets. If a trust with $100,000 incurs an annual fee of $3,500, your hard-earned estate will benefit the trustee as much as your heirs. A trust probably doesn't make financial sense if the total fees exceed 2%.Check Out Our Best Services for Investors
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The beautiful American flag sure represent all of the freedom. This was taken one evening while the moon was rising. The American flag, a symbol of freedom. The flag is freedom to those who fight for it, to those who die for it, even to those who burn it. The American flag is a symbol of freedom, liberty and human rights. It is a symbol of our home and all that we believe in. A symbol men rally behind, whether on our shores or foreign shores.
I am a retired teacher, coach and athletic director. While my wife, Judy, and I were teaching she had a photo studio, and I had a dark room where I did black and white and color. Some was for the studio while most of it was just a hobby. When we retired in 2000, we sold our house in Eastern Washington and moved onto our boat, Last Class, and our motorhome. We sold Last Class a few years ago and bought a small house in Yuma, Arizona and this year bought one in Emmett Idaho. Now we spend the summers in Emmett and the winters in Yuma. Over our 50 years of marriage, we have always had an interest in photography and still do. You may order any unframed photo from this website. Just email me at firstname.lastname@example.com the name of the photo...
Our return policy is very simple:
If you're not happy with a purchase that you made on FineArtAmerica.com, for any reason, you can return it to us within 30 days of the order date. As soon as it arrives, we'll issue a full refund for the entire purchase price. Please note - Fine Art America does not reimburse the outgoing or return shipping charges unless the return is due to a defect in quality.
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Click the links to see all of my Redbubble Love Paintings, Love Photography, Love Greeting Cards, Love Stickers, Love Tees, , and Love T-Shirts at Arttowear
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*My Images Do Not Belong To The Public Domain. All images are copyright © taiche. All Rights Reserved. Copying, altering, displaying or redistribution of any of these images without written permission from the artist is strictly prohibited -——————————————————————————————————————————————————
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AMERICA/COLOMBIA - After the Bishops also international organizations denounce the serious situation in Chocò
Chocò (Agenzia Fides) - The representative in Colombia of the High Commissioner of Human Rights of the United Nations, Todd Howland, Bishop of the Diocese of Quibdó, Mgr. Juan Barreto, the "Defensor del Pueblo", Jorge Armando Otàlora, and representatives of indigenous peoples and Afro-descendants, have denounced the Colombian government and the international community for the violation of human rights and the humanitarian crisis that the Chocò region of Colombia is experiencing. During the works of the Episcopal Conference of Colombia, on July 8, the Bishops of the region had described the plight the area lives (see Fides 09/07/2014).
The most worrying is the amount of people fleeing from the region: in the first half of 2014, 4,000 have already left. The note sent to Fides by Caracol Radio reports the thought of Todd Howland, representative of the UN High Commissioner for Human Rights, on the strategy that the Colombian government should follow in order to put an end to this crisis that has forced 32,000 people to leave their land. "I believe in the importance of proposing persons within the national government with direct access to ministers - said Howland - who in turn have access to the president".
One thing is emblematic: In Chocò 80% of the population does not have drinking water or sanitation.
The Bishop of Quibdó, Mgr. Juan Barreto, has urged the national government to assist the department of Chocò in a special way: "surely the government has already made an effort to invest in the area, but the results are still not seen in the population (see Fides 09/07/2014). In Chocò illegal groups are present everywhere, illegal mining and illicit crops have increased". According to the note sent to Fides, Mgr. Barreto addressed the guerrillas directly with these words: "You have to recognize that you are a problem for the population, people consider you a menace". (CE) (Agenzia Fides 11/07/2014)
- 2015-02-21 - Lent: multimedia "On the way to Easter"
- 2015-02-10 - The proposal of the FARC divides public opinion
- 2015-01-29 - Nearly 50 000 children victims of homicide because of armed conflict
- 2015-01-26 - We need leaders who are committed and not "deaf and dumb authorities" says Mgr. Epalza
- 2014-12-22 - Even from pain comes the hope of peace, the process continues
- 2014-12-18 - For Mgr. Falla Robles: "The unilateral cease-fire should take place without any conditions"
- 2014-12-13 - SOS of the Bishop on the proliferation of dengue fever
- 2014-12-05 - Peace talks resume December 10
- 2014-12-02 - Satisfaction for the release of the General, but it is necessary to resume talks for a definite peace
- 2014-12-01 - Children are half of the victims of landmines and prohibited explosive devices


text:
I was testing my blog reader application at my friends house (on my laptop) and it connected to the network and the parsing of all the JSON worked great. As soon as I get home I go to test it and it can't seem to connect to a Network. My laptop is connected to my internet (no issues with browsing internet) and my emulator does not have airplane mode on.
Also apparently my LogCat decided to go on vacation because it is not outputting ANY info at all.
the console has been outputting this
[2013-08-29 19:43:24 - BlogReader] Android Launch!
[2013-08-29 19:43:24 - BlogReader] adb is running normally.
[2013-08-29 19:43:24 - BlogReader] Performing com.practice.blogreader.MainListActivity activity launch
[2013-08-29 19:43:25 - BlogReader] Automatic Target Mode: using existing emulator 'emulator-5554' running compatible AVD 'Nexus_4_Emulator'
[2013-08-29 19:43:26 - BlogReader] Application already deployed. No need to reinstall.
[2013-08-29 19:43:26 - BlogReader] Starting activity com.practice.blogreader.MainListActivity on device emulator-5554
[2013-08-29 19:43:27 - BlogReader] ActivityManager: Starting: Intent { act=android.intent.action.MAIN cat=[android.intent.category.LAUNCHER] cmp=com.practice.blogreader/.MainListActivity }
[2013-08-29 19:43:27 - BlogReader] ActivityManager: Warning: Activity not started, its current task has been brought to the front
Even though the only thing that is displayed on the emulator is the application.
Any Ideas?


text:
My Cart
Store Locator
VIP Membership Terms: Normally $24.99 per year, but your Web Exclusive deal means you enjoy 3 months of VIP Family Benefits for $1.99. Check out your savings and benefits below.
Cancellation: Rest assured you can cancel your new membership at any time during the year at a pro-rated rate, simply call your VIP Hotline at 800.543.7309 or click here to submit your cancellation request. Benefits and prices are subject to change.
Want more info? Click here and read 'til your heart's content or call your VIP Hotline at 800.543.7309
Mens ASICS Conquest Wrestling Singlet UniSuits - Navy M
Available in Navy
Men's ASICS� Conquest Wrestling Singlet :: Conquest says it all. This is a singlet for winners, designed by winners. Everything about this design -- flatlock stitching, muscle-supporting gradient design, anti-odor fabric -- optimizes performance. This web exclusive item ships separately within the continental U.S. only. You can count on this ...
Mens ASICS Favorite Sleeveless Technical Tops - Green Gecko L
Available in Green Gecko
Men's ASICS� Favorite? Sleeveless :: Our ASICS� exclusive fabric is super lightweight; keeps your potentially offensive b.o. at bay with quick-dry/anti-odor tech; keeps the sun off your back with a permanent 50&43;UPF rating; and gives you some much-needed ventilation with mesh panels in all the right places. This web exclusive ...
Mens ASICS Favorite Short Sleeve Technical Tops - Slate M
Available in Slate
Men's ASICS� Favorite? Short Sleeve :: The ASICS� Favorite? Short Sleeve top is back, and lighter than ever; with built-in quick-dry/anti-odor/50+UPF functionality assures you won't be wilting any flowers and helps you save money on that huge sunscreen bill you've been building up. This web exclusive item ships separately within ...
Mens ASICS ASX Brief Underwear Bottoms - Charcoal S/M
Available in Charcoal
Men's ASICS� ASX BRIEF :: Feel supported in all you do with your ASICS� ASX? Brief. Get what you need, where you need it most with this brief's tailor-made, strategic compression design, and protect your skin from chafe in the seam-free fabric. Never worry about funky smells spoiling your fun ...


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The Dark Knight reigns supreme!
The Dark Knight is an excellant picture.People need to get past Bale's grummbling voice. Bale is the best Batman on terms of his fighting techniques and is a good Bruce Wayne. The movie is fast paced and has action around every corner.Batman isn't the individual that makes this movie great. It is the Joker! Heath Ledger made a smashing performance right before he kicked the bucket. Joker was an entertaining character to watch in the movie. He made the character believeable. He was played dead on. Two-Face was done decently in this movie. The movie never became boring. The only problem besides the grumble voice is that Batman had to hard a time fighting of attack dogs. 4 and 1/2 stars!


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Metro Union Members Re-Elect Mike Breihan
Members of Amalgamated Transit Union Local 788 Thursday re-elected Mike Breihan to another three year term.
Larry Rice: Metro's Bench Dividers Symbolize War Against Homeless
A move by the St. Louis-area mass transit agency Metro will make it harder for homeless people to nap on bus shelter benches downtown, a move that has angered some advocates for the homeless.
No Napping Here: Metro Adds Dividers To Bus Shelter Benches
"[They'll] discourage people from taking up the entire space with their packages and their bags or even by lying down," a spokeswoman explains.
"Apple Picking" Latest Crime Trend To Hit St. Louis Area
Apple iPhones and other expensive devices being targeted by robbers.
Holiday Magic Train To Be Launched By MetroLink This Weekend
The "Kingsbury Place Singers" dressed in Victorian era garb greeted passengers Tuesday with the sounds of the season.
St. Louis Metro Buses No Longer Taking Some Coins
Starting next Monday, Metro will no longer accept pennies, 50-cent coins or $2 bills as payment.
Metro, Transit Union to Resume Talks This Week
"One of us has to bend," Amalgamated Transit Union Local 788 President Mike Breihan said. "I'm willing to bend a little bit if they're willing to bend a little bit. We both have to give a little bit."
Metro Transit Workers Vote To Authorize Strike
Amalgamated Transit Local 788 authorized a strike Tuesday, but it does not mean a strike is immanent.
Metro Considers E-Cig Ban On Buses & Trains
Health experts still working to verify manufacturers' claims of E-cig safety.
Ground Broken In Sauget For New FedEx Ground Distribution Center
Will employ more than 100 and move 10,000 package an hour when it opens next year.


text:
Product Description
Available while supplies last.
This wall sconce by Philips is offered in a satin nickel finish. Features etched white glass. Works with an LED light source.
LED wall sconce with etched white glass.
- 10.5w LED
- LEDs have 50,000 hours of usable life.
- Dimmable with low-voltage electronic dimmer.
- 1000 lumens (initial), 3000K, 80CRI.
Finish: | Satin Nickel | |
Glass: | Etched White | |
Light Bulb: | LED | |
Installation: | Dry Locations [Explain] | |
Listing: | , Eco-Friendly, LED, Energy Saving | |
Shade Material | Glass Shades | |
Number of Lights Refers to the number of lights on a given fixture. Choose from a wide variety of different fixtures ranging from 1 - 6+ lights. | Number of Lights | 1-Light |
Bulb is included free
Bulbs are not eligible for replacement
Bulbs are not eligible for replacement
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Mfr Part # | |
Sku | |
Group # | 2193245 |
Category | Wall Sconces - 92 |
Style | Modern - 3 |
Sales Rank | 108 |
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text:
Om Brew Yoga is a very unique yoga program that is the brainchild of two non conventional yogis. Shelah began working toward her RYT instructor training in 2012 and noticed quickly that the yoga world was missing out on a very unique and amazingly awesome dynamic – NORMAL people. Moms, Dads, teens, single guys, beer lovers, couch potatoes, the inflexible people of the world, people with a bit more fluff to their bods.
Once Shelah began teaching, her husband, Jeffrey noticed that the yoga community was missing out on a key element that HE loved most – FUN. Together, they saw a vision of a yoga experience that could be WELCOMING and FUN for every single person out in the big bad world. And while locked in the car together for several hours on a family road trip – Om Brew Yoga was born.
People often ask us what Om Brew Yoga is. It isn't a style of yoga. It is however the attitude that we try to convey in all of our classes. We are passionate about yoga and how great it is for our health and well-being. We are also pretty passionate about enjoying the life that we have been given – so we combined the passion and the fun into one pretty kick ass way of getting bendy.
Om Brew Yoga was initially introduced to the area coupled with this couple's other passion – Craft beer.
Introducing yoga in the area breweries was a way for us to disarm people. It allowed us to knock down some of the walls that people had up regarding what they thought yoga was or should be. You can't possibly have an idea in your head about what you are supposed to think or feel about something if your initial experience happens at someplace completely unexpected.
We love people and we love helping people to open up their minds to new experiences. Being able to bring yoga to people in such a fun way has really been a dream for us.
Initially, when Shelah first experienced yoga, she was just starting her own health journey. She was well over 250 pounds at the time and yoga was a struggle physically as well as emotionally.
I knew that I needed yoga but that didn't make it any easier to take that first step into the studio. I was intimidated. I cried on my mat – a lot. I felt like I didn't belong and I didn't deserve to be there. Reality is, I needed those classes and that experience just as much as anyone. I recall feeling invisible in the classes though, because the instructor would barely even look at me during the class. No alignment help. No suggestions to make things more comfortable. She just pretended that I didn't exist.
That feeling of not belonging is exactly what Shelah has been striving to eliminate within the yoga community. She teaches in a light hearted and fun way and her passion for connecting with people really shines through in her classes, where there are often dancing breaks, beer breaks and high fives happening along with plenty of laughter.
Shelah is currently leading yoga practices throughout the South Florida area. Her classes all encompass her unique style of teaching and she welcomes EVERYONE in the door of each location where she is invited to teach. If you would like to come experience Shelah, Jeffrey and Om Brew Yoga, please check the calendar below. Each location offers its own unique experience so be sure to read the fine print.
Om Brew in the News
Our Om Brew Program just garnered national attention as a featured article on GM's Drive the District site:
Check out the awesome article published in the Broward New Times about our Om Brew Program.
Listen to our segment that was featured on NPR.
We have been featured in the Sun Sentinel too!
Want to bring Om Brew to your Event or Facility?
- Event promotion
- Payment collection
- Event registration
- Liability release forms
- Music
- Lead a high energy yoga class


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Tue, December 11, 2007 - 9:42 AM
December 12, 2007
The first time I heard her music, it spoke to my soul. I twas quite like wandering in unknown territory until, in the distance you hear the song, another wolf howling... If I could make music like that... Well, she has a purpose and destiny. Beloved dragonslayer, you sing my spirit into being. And I thank you.


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Healthy Recipes
Smoothies for Good Health
My husband's teenage sisters are going through a smoothie phase; they are obsessed with blending everything and anything at all times. They've been concocting many smoothies recently. I suggested they try to balance the sugar levels (by avoiding too much sucrose) and pack the drinks with superfoods and antioxidants from fresh fruits and veggies. Extra nutrients such as flax or chia seeds are a plus.
I've gathered a long list of kid-friendly smoothies for the girls and you to see. Please keep in mind, especially at a young age, the purpose of the drink is to feel good, improve your helth (without necessarily having the focus of weight loss), get a glowing skin and of course, enjoy a delicious treat!
Full Recipe...
Fried Wonton Tofu Recipe
The next few days mark the beginning of the Vietnamese Tết celebrations. A tradition of Tết is that you eat vegetarian (ăn chay) on the last day of the previous year and first day of Asian New Year, so I will be sharing several Vietnamese vegetarian dishes with you until the celebration commences.
I prepared a tofu dish that included a typical Vietnamese vegetable called trái su su in Vietnamese. It's also known as chayote in English, christophine in Creole and French and it's from the squash family. So as you can imagine, if not cooked over high heat (to allow as much liquid to evaporate as possible), the dish can become very watery and soggy. To balance the texture of the dish, I added crispiness by crumbling fried wonton wrappers.
Full Recipe...
Crookneck Squash Gemelli Pasta (Vegetarian Pasta Recipe)
It's Meatless Monday and today I'm sharing with you one of baby Aria's favorite pasta dishes. I used gemelli pasta, cut crookneck squash the same size as the pasta and flavored them with tarragon and parsley crème fraîche. The crookneck squash provides a soft texture to the dish and the same-sized pieces make for easy eating, especially for little ones.
I hope your weekend was as adventuresome as ours. We spent the weekend at Half Moon Bay State Beach. It wasn't too hot with the ocean breeze. It was so peaceful and quiet; exactly what we needed! Aria and I wandered along the beaches and on the trails after our picnic. I had prepared my husband Lulu's favorite cucumber tea sandwiches and used the remaining filling to flavor the pasta dish the following day!
Full Recipe...
Coconut Tofu Recipe
Eating vegan foods doesn't necessarily mean they have to be bland. My goal to jazz up a Japanese eggplant and broccoli tofu dish was to add extra richness to the taste with coconut cream. The vegetables cooked fairly quickly, so I focused more on seasoning the sauce, using soy sauce, chile black bean sauce, palm sugar and coconut.
This coconut tofu is a great way for our family (baby Aria and I are the only ones not on a vegetarian diet) to share the same meal without missing meat. The tofu was flavorful with crispy texture and the added spiciness. With a dish like this one, you won't have naysayers claiming the tofu dish is too plain!
Full Recipe...
Tri-Color Green Bean Salad Recipe
At this time of the year I think I've reached the last crop of green beans to harvest from our garden. I simply steamed them and served them the healthy way. In addition to regular green beans, I bought fresh purple beans and wax beans to complete the dish.
I seasoned the steamed bean salad with a sauce that I concocted using green beans, sweet basil, almond powder and fruity olive oil. As a reminder of the sauce flavor, I garnished the salad with lightly toasted sliced almonds.
Full Recipe...


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Do career research and find in-depth salary data for specific jobs, employers, schools, and more. Know what you're looking for? Start a search below, browse to discover or Get a free, personal salary report »
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Median Salary: $24,000
"An accountant will spend most of the time within an office setting."
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Country Manager
Median Salary: $48,521
"A country manager oversees the operations of a global company within a specific country."
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"General/operations managers are responsible for maintaining a business."
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Median Salary: $16,000
"Human resources (HR) managers work with a team of professionals to support a company's growth and operation."
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Median Salary: $23,331
"Information technology (IT) project managers lead their technical team(s) in design and development tasks."
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Median Salary: $14,400
"The Project Manager of Software Development is a position in high demand in today's technical world."
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"Software developers are the people who create the different programs that computers use for everything they do."
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"A software engineer is responsible developing and maintaining software applications and/or systems that function reliably and efficiently."
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Before you show up for a job interview, do your homework. See how different employers pay, how satisfied their employees are and what it's really like to work there.
Whether you're choosing a school or degree or simply curious about your alma mater, we'll show you career outcomes by either college or major. Browse all schools or degrees »
RMIT University
$4,200 - $34,800
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$23,583 - $66,757
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We've got serious career advice, with a side of sass, on careers, salary negotiation and professional growth – and the data to back it up. The world of work has changed dramatically. The same old career advice just doesn't cut it.
Is It Better to Stand Out at Work, or to Hide? So, you've got a job. You can breathe a sigh of relief. And, for some workers, just having a job is enough. You're hearing all that great news about t... Read More |
PayScale's 2015 College ROI Report: Will Your Degree Pay Off? Student loan debt has more than quadrupled over the past 20 years, according to Pew Research Center. In 2012, the average loan total was $29,400, and ... Read More |
5 Takeaways From One Teacher's Social Media Experiment for Her Students One Minnesota high school teacher, Michelle Van Bibber of Stewartville High School, decided to teach her students a valuable lesson about over-sharing... Read More |
Vince Vaughn's Stock Photos Perfectly Capture the Excitement of Modern Corporate Life If you've ever read a single blog post about career development, job searching, or any other aspect of working for a living, you've seen them: corpora... Read More |
6 Signs You're Running a Bad Meeting People don't like being in meetings, and that makes it really difficult to host a good one. But, at least for now, they are still a necessary evil for... Read More |
3 Ways to Deal With an Offensive Co-worker Who Just Doesn't Get It In the workplace, there's a fine line between joking around and being offensive -- and there's always that one co-worker who just doesn't seem to get ... Read More |
Tell us about your current job and your skillset, and we'll let you know how much employers are paying in your area.


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Something to watch for. Contour has already been awesome in responding (on Thanksgiving no less) and getting it taken care of but make sure inspect the camera every now and again.
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RPGFan Music
Game Music Festival 2013
Mike Salbato
, with contributions from
Andrew Barker
Luna Lee
, and
John Tucker
November 29, 2013
– By now, you know that we love music here at RPGFan. Enough so that after reviewing hundreds of soundtracks, we finally rebranded the section
RPGFan Music
, which even has its own podcast,
Rhythm Encounter
. When we learned that Loudr was hosting a
Game Music Festival
this weekend and we had an opportunity to be a part of it, of coruse we were on board. Celebrate independent artists, showcase their works, and talk to a few of them? How could we say no?
What you'll find here are interviews with three musicians you may be familiar with: Zack Parrish, who composed the excellent soundtrack to Valdis Story: Abyssal City. Next is TPR, who has so far released four albums of Final Fantasy music arranged in a slow, moody, 'melancholy' style. Finally, we talk once again with Kan Gao, creator and composer of indie darling To The Moon about his next endeavors.
Additionally, we have the debut of three album reviews that will be available at special Festival-only prices. Erutan's A Bard's Side Quest, a collection of vocal arrangements from some of the best music in the RPG world is new to RPGFan, as are the soundtracks to Acts I & II of surreal graphic adventure Kentucky Route Zero.
This RPGFan feature was made possible thanks to the fine folks at
. Be sure to check out the
Game Music Festival website
for more interviews, commentaries, and special limited-time deals on album collections by the artists here and more!
We also offer sincere thanks to the artists that took the time to chat with us; you guys are great.
Featured Interviews & Reviews
Zack Parrish
Valdis Story: Abyssal City
Melancholy FF Albums
Kan Gao
To The Moon, A Bird Story
Featured Album Reviews:
Kentucky Route Zero
Act I
Kentucky Route Zero
Act II
A Bard's Side Quest
Vocal Arrangements
Featured Content
Aurion: Legacy of the Kori-Odan
Hands-On Preview
Final Symphony
Music Review
J.U.L.I.A. Among the Stars
The Book of Unwritten Tales 2
Life is Strange: Episode 1
Hand of Fate
Random Encounter Episode 91
RSS Feeds & More
Complete Feed
Reviews Feed
Media Feed
Random Encounter
Random on iTunes
Rhythm Encounter
Rhythm on iTunes


text:
School Holiday Program
Looking for activities these school holidays?
Click on the link for information on our school holiday program at Lefevre Community Stadium.
The City of Port Adelaide Enfield is committed to giving young people opportunities, information and support. We strive to make the local area a great place for young people to work, live, study or play in.
This website aims to connect young people to a wide range of activities, events, projects, services and information as well giving you the opportunity to have input into what happens in your local area.


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Limited-time feature
34 year old woman | Plano, TX, USA | Seeking men 30-37 within 10 miles
Let's keep it simple
I am smart, witty, responsible, loyal, and I'm normally a planner with the occasional sponteneity. I like to read, travel when I have a chance, watch movies, do pilates, eat out in restaurants, and do the occasional nature walk. I am looking for someone who's smart; confident without being egotistical; funny without pushing off seriousness; caring; and more or less neat and clean with surroundings and possessions, but not materialistic.
Coffee and conversation , Cooking , Dining out , Movies/Videos , Exploring new areas , Travel/Sightseeing , Volunteering
Aerobics, Other types of exercise, Walking / Hiking, Yoga
I exercise 3-4 times per week.
I have Cats
I like Dogs, Horses
I have a cat that is not staying with me at the moment. This may change in the near future.
Middle of the Road
I am reading Mexican Enough. My last book read was Kinky Gazpacho, and the one before that was Garden of Beasts. I try to read at least one book a month.
Her | What she is looking for | |
Appearance | ||
Height: | 5'8" (172cms) | 5'10" (177cms) to 7'3" (220cms) |
Body type: | About average | No preference |
Eyes: | Blue | No preference |
Hair: | Dark blonde | No preference |
Lifestyle | ||
Smoke: | No Way | No Way |
Drink: | Never | Never |
Occupation: | I'll tell you later | No preference |
Income: | I'll tell you later | $35,001 to $50,000, $50,001 to $75,000, $75,001 to $100,000, $100,001 to $150,000, $150,001+ |
Relationship: | Never Married | No preference |
Have kids: | No | No preference |
Wants kids: | Probably not | Someday, Not sure, Probably not, No |
Background | ||
Ethnicity: | White / Caucasian | No preference |
Faith: | Spiritual but not religious | Agnostic, Atheist, Christian / Catholic, Christian / LDS, Christian / Protestant, Spiritual but not religious, Christian / Other |
Languages: | English, Spanish | English, Spanish |
Education: | Graduate degree | Some college, Associates degree, Bachelors degree, Graduate degree, PhD / Post Doctoral |