Lfng-expressing centroacinar cell is a unique cell-of-origin for p53 deficient pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with limited understanding of etiology. Studies in mice showed that both acinar and ductal cells of the pancreas can be targeted by combination of oncogenic Kras and p53 mutations to form PDAC. How the transforming capacities of pancreatic cells are constrained, and whether a subset of cells could serve as a prime target for oncogenic transformation, remain obscure.

Notch signaling pathway in pancreatic tumorigenesis.

The Notch signaling pathway is an evolutionary conserved signal transduction cascade that is critical to embryonic and postnatal development, but aberrant Notch signaling is also implicated in tumorigenesis of many organs including the pancreas. Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy in the pancreas, with a dismally low survival rate due to the late-stage diagnosis and peculiar therapeutic resistance. Upregulation of the Notch signaling pathway has been found in preneoplastic lesions as well as PDACs in genetically engineered mouse models and human patients, and inhibition of the Notch signaling suppresses tumor development and progression in mice as well as patient-derived xenograft tumor growth, suggesting a critical role for Notch in PDAC.

A tumor-suppressive function for Notch3 in the parous mammary gland.

Notch3 promotes mammary luminal cell specification and forced Notch3 activation can induce mammary tumor formation. However, recent studies suggest a tumor-suppressive role for Notch3. Here, we report on Notch3 expression and functional analysis in the mouse mammary gland.

Loss of cooperates with oncogenic to induce pancreatic cystic neoplasms.

Notch signaling exerts both oncogenic and tumor-suppressive functions in the pancreas. In this study, deletion of in conjunction with oncogenic expression in the mouse pancreas induced rapid development of acinar-to-ductal metaplasia and early stage pancreatic intraepithelial neoplasm; however, culminating in cystic neoplasms rather than ductal adenocarcinoma. Most cystic lesions in these mice were reminiscent of serous cystic neoplasm, and the rest resembled intraductal papillary mucinous neoplasm.

PIK3CG Is a Potential Therapeutic Target in Androgen Receptor-Indifferent Metastatic Prostate Cancer.

The prostate epithelium consists of predominantly luminal cells that express androgen receptor and require androgens for growth. As a consequence, the depletion of testicular androgens in patients with prostate cancer results in tumor regression. However, it eventually leads to a castration-resistant disease that is highly metastatic.

Downregulation of Notch Signaling in Kras-Induced Gastric Metaplasia.

Activating mutations and amplification of Kras and, more frequently, signatures for Kras activation are noted in stomach cancer. Expression of mutant Kras in the mouse gastric mucosa has been shown to induce hyperplasia and metaplasia. However, the mechanisms by which Kras activation leads to gastric metaplasia are not fully understood.

Kras upregulates Notch signaling to induce gallbladder tumorigenesis in mice.

Background: Kras mutations and increased Notch activation occur frequently in gallbladder cancer. However, their roles in gallbladder carcinogenesis have not been defined. This study was aimed at determining whether expression of mutant Kras was sufficient to induce gallbladder carcinoma and whether Notch deregulation played a role in this context.

Lunatic Fringe and p53 Cooperatively Suppress Mesenchymal Stem-Like Breast Cancer.

Claudin-low breast cancer (CLBC) is a poor prognosis molecular subtype showing stemness and mesenchymal features. We previously discovered that deletion of a Notch signaling modulator, Lunatic Fringe (Lfng), in the mouse mammary gland induced a subset of tumors resembling CLBC. Here we report that deletion of one copy of p53 on this background not only accelerated mammary tumor development but also led to a complete penetrance of the mesenchymal stem-like phenotype.

Manic fringe promotes a claudin-low breast cancer phenotype through notch-mediated PIK3CG induction.

Claudin-low breast cancer (CLBC) is a poor prognosis disease biologically characterized by stemness and mesenchymal features. These tumors disproportionately affect younger patients and women with African ancestry, causing significant morbidity and mortality, and no effective targeted therapy exists at present. CLBC is thought to originate from mammary stem cells, but little is known on how or why these tumors express a stable epithelial-to-mesenchymal transition phenotype, or what are the driving forces of this disease.

AKT and 14-3-3 regulate Notch4 nuclear localization.

Members of the Notch family of transmembrane receptors, Notch1-4 in mammals, are involved in the regulation of cell fate decisions and cell proliferation in various organisms. The Notch4 isoform, which is specific to mammals, was originally identified as a viral oncogene in mice, Int3, able to initiate mammary tumors. In humans, Notch4 expression appears to be associated with breast cancer stem cells and endocrine resistance.

Tumor-suppressive activity of Lunatic Fringe in prostate through differential modulation of Notch receptor activation.

Elevated Notch ligand and receptor expression has been associated with aggressive forms of prostate cancer, suggesting a role for Notch signaling in regulation of prostate tumor initiation and progression. Here, we report a critical role for Lunatic Fringe (Lfng), which encodes an O-fucosylpeptide 3-ß-N-acetylglucosaminyltransferase known to modify epidermal growth factor repeats of Notch receptor proteins, in regulation of prostate epithelial differentiation and proliferation, as well as in prostate tumor suppression. Deletion of Lfng in mice caused altered Notch activation in the prostate, associated with elevated accumulation of Notch1, Notch2, and Notch4 intracellular domains, decreased levels of the putative Notch3 intracellular fragment, as well as increased expression of Hes1, Hes5, and Hey2.

Targeting Met and Notch in the Lfng-deficient, Met-amplified triple-negative breast cancer.

Triple negative breast cancer (TNBC) accounts for 15-20% of breast carcinomas and represents one of the most aggressive forms of this disease. Basal and claudin-low are the two main molecular subtypes among TNBCs. We previously reported that deletion of Lfng in mouse mammary gland caused deregulated Notch activation and induced basal-like and claudin-low tumors with co-selection for Met amplification.

Sirt2 deacetylase is a novel AKT binding partner critical for AKT activation by insulin.

AKT/PKB kinases transmit insulin and growth factor signals downstream of phosphatidylinositol 3-kinase (PI3K). AKT activation involves phosphorylation at two residues, Thr(308) and Ser(473), mediated by PDK1 and the mammalian target of rapamycin complex 2 (mTORC2), respectively. Impaired AKT activation is a key factor in metabolic disorders involving insulin resistance, whereas hyperactivation of AKT is linked to cancer pathogenesis.

Historical overview of Taenia asiatica in Taiwan.

An overview of the epidemiological, biological, and clinical studies of Taenia and taeniasis in Taiwan for the past century is presented. The phenomenal observations that led to the discovery of Taenia asiatica as a new species, which differ from Taenia solium and Taenia saginata, are described. Parasitological surveys of the aborigines in Taiwan revealed a high prevalence of taeniasis, which might be due to the culture of eating raw liver of hunted wild boars.

The dog mite, Demodex canis: prevalence, fungal co-infection, reactions to light, and hair follicle apoptosis.

Infection rate, reaction to light, and hair follicle apoptosis are examined in the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013) prevalence of D.

Prevention of bronchial hyperplasia by EGFR pathway inhibitors in an organotypic culture model.

Lung cancer is the leading cause of cancer-related mortality worldwide. Early detection or prevention strategies are urgently needed to increase survival. Hyperplasia is the first morphologic change that occurs in the bronchial epithelium during lung cancer development, followed by squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumor.

CREB mediates prostaglandin F2alpha-induced MUC5AC overexpression.

Mucus secretion is an important protective mechanism for the luminal lining of open tubular organs, but mucin overproduction in the respiratory tract can exacerbate the inflammatory process and cause airway obstruction. Production of MUC5AC, a predominant gel-forming mucin secreted by airway epithelia, can be induced by various inflammatory mediators such as prostaglandins. The two major prostaglandins involved in inflammation are PGE(2) and PGF(2alpha).

Cyclic AMP-responsive element binding protein- and nuclear factor-kappaB-regulated CXC chemokine gene expression in lung carcinogenesis.

The recognition of the importance of angiogenesis in tumor progression has led to the development of antiangiogenesis as a new strategy for cancer treatment and prevention. By modulating tumor microenvironment and inducing angiogenesis, the proinflammatory cytokine interleukine (IL)-1beta has been reported to promote tumor development. However, the factors mediating IL-1beta-induced angiogenesis in non-small cell lung cancer (NSCLC) and the regulation of these angiogenic factors by IL-1beta are less clear.

Infection of normal C3H/HeN mice with Taenia saginata asiatica oncospheres.

Normal C3H/HeN female mice were used to develop an animal model of Taenia saginata asiatica oncosphere infection. The host cellular immune response in this model was analyzed by a cytokine enzyme-linked immunosorbent assay (cytokine ELISA) and flow cytometry. Tumor-like cysts containing cysticerci were recovered from the inoculation sites of female mice 7 weeks postinfection with the T.

Growth suppression of lung cancer cells by targeting cyclic AMP response element-binding protein.

Genes regulated by cyclic AMP-response element-binding protein (CREB) have been reported to suppress apoptosis, induce cell proliferation, and mediate inflammation and tumor metastasis. However, it is not clear whether CREB is critically involved in lung carcinogenesis. We found that non-small cell lung cancer (NSCLC) cell lines exhibited elevated constitutive activity in CREB, in its immediate upstream kinases (ribosomal s6 kinase and extracellular signal kinase), and in the CREB-regulated cell survival proteins Bcl-2 and Bcl-xL.

Regulation of mucin gene expression by CREB via a nonclassical retinoic acid signaling pathway.

Vitamin A and its metabolite retinoic acid (RA) are essential elements for normal lung development and the differentiation of lung epithelial cells. We previously showed that RA rapidly activated cyclic AMP response element-binding protein (CREB) in a nonclassical manner in normal human tracheobronchial epithelial (NHTBE) cells. In the present study, we further demonstrated that this nonclassical signaling of RA on the activation of CREB plays a critical role in regulating the expression of airway epithelial cell differentiation markers, the MUC2, MUC5AC, and MUC5B genes.

Prevalence of antibodies to Toxoplasma gondii in pigeons (Columba livia) in Taiwan.

Starting from January 2004 to December 2004, 665 blood serum samples from pigeons (Columba livia) were collected from 44 pigeonaries in 11 counties and 20 regions in Taiwan. These samples were examined by latex agglutination test (LAT) for antibodies to Toxoplasma gondii by using the LAT. Antibodies were found in 4.

Human intestinal capillariasis (Capillaria philippinensis) in Taiwan.

Capillaria philippinensis was first reported in 1963 in the Philippines. Major outbreaks have occurred in the Philippines and Thailand. This article reviews the known 30 intestinal capillariasis cases in Taiwan from January 1983 to December 2003.