Glucagon-like peptide 1 (GLP-1) is known to suppress glucagon secretion, but the mechanism by which GLP-1 exerts this effect unclear. In study, we demonstrated receptor (GLP-1R) expression in α-cells using both antibody-dependent and antibody-independent strategies. A novel α-cell–specific GLP-1R knockout (αGLP-1R−/−) mouse model was created used investigate its effects on secretion glucose metabolism. Male female αGLP-1R−/− mice showed higher nonfasting levels than their wild-type...

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a dismal prognosis. Currently, there no effective therapy for PDAC, and detailed molecular functional evaluation of PDACs needed to identify develop better therapeutic strategies. Here we show that the transcription factor Krüppel-like 7 (KLF7) overexpressed in PDACs, inhibition KLF7 blocks PDAC tumor growth metastasis cell culture mice. expression can be up-regulated due activation MAP kinase pathway or inactivation...

BACKGROUND Extravasation is a critical step in cancer metastasis, which adhesion of intravascular cells to the vascular endothelial controlled by cell surface molecules. The role interleukin‐17 (IL‐17), insulin, and insulin‐like growth factor 1 (IGF1) prostate unknown, subject present study. METHODS Human umbilical vein (HUVECs) human lines (PC‐3, DU‐145, LNCaP, C4–2B) were analyzed for expression molecule (VCAM‐1), integrins, cluster differentiation 44 (CD44) using flow cytometry Western...

BRAF inhibitors (BRAFi) have been approved for the clinical treatment of BRAF-mutant metastatic melanoma. Although initial responses to BRAFi are generally favorable, acquired resistance emerges rapidly, resulting in failure. Only some underlying mechanisms responsible currently understood. Here, we showed that genetic inhibition histone acetyltransferase 1 (HAT1) melanoma cells resulted resistance. Using quantitative immunofluorescence analysis patient sample pairs, consisting pre-treatment...

Despite conflicting results, there is evidence to suggest an inverse link between total body cholesterol levels and the risk of certain malignancies. Based on previous reports, this phenomenon appears vary with cancer site, and, in particular, more consistent data relations was reported gastric cancer. In current study, effect cell viability examined using vitro culture system. Addition medium resulted reduced clonogenicity SNU601, SNU638 SNU216 cells by induction both autophagic apoptotic...

The ether phospholipid edelfosine is the prototype of a group synthetic antitumor alkyllysophospholipid (ALP) compounds that exert pro-apoptotic effects in various types cancer cells through cell type-dependent mechanisms. In this study, we examined effect human gastric cells. Edelfosine decreased viability and induced autophagic death at moderate concentration (~30 μM), whereas it apoptotic concentrations over 30 μM. Interestingly, low (5-10 μM) effectively enhanced recombinant tumor...

BACKGROUND Bone metastasis from primary prostate cancer leads to markedly diminished quality of life with poor long-term survival. seeking treatment options are limited adverse consequences on rapidly proliferating tissues such as bone marrow. In the present study, we seek determine bone-enriching capabilities monomethyl auristatin E phosphate (MMAEp), a derivative potent antimitotic (MMAE). METHODS The in vitro actions and mechanisms cytotoxicity were assessed using cell viability,...

Prostate cancer (PCa) is one the most common malignancies in men. The high incidence of bone metastasis years after primary therapy suggests that disseminated tumor cells must become dormant, but maintain their ability to proliferate marrow. Abscisic acid (ABA) a stress response molecule best known for its regulation seed germination, stomal opening, root shoot growth and other responses plants. ABA also synthesized by mammalian has been linked human disease. aim present study was examine...

Aminomethylphosphonic acid (AMPA) and its parent compound herbicide glyphosate are analogs to glycine, which have been reported inhibit proliferation promote apoptosis of cancer cells, but not normal cells. Methoxyacetic (MAA) is the active metabolite ester phthalates widely used in industry as gelling, viscosity stabilizer; exposure associated with developmental reproductive toxicities both rodents humans. MAA has suppress prostate cell growth by inducing arrest apoptosis. However, it...

// Keshab Raj Parajuli 1 , Qiuyang Zhang Sen Liu Zongbing You 1, 2, 3, 4, 5 Departments of Structural & Cellular Biology, Tulane University, New Orleans, Louisiana 70112, USA 2 Department Orthopaedic Surgery, 3 Cancer Center and Research Consortium, 4 for Stem Cell Regenerative Medicine, Aging, Correspondence to: You, e-mail: zyou@tulane.edu Keywords: aminomethylphosphonic acid, glyphosate, prostate cancer, metastasis, orthotopic xenograft mouse model Received: October 01, 2015 Accepted:...

Aim: Type II diabetes (T2D) stems from insulin resistance, with β-cell dysfunction as a hallmark in its progression. Studies reveal that β cells undergo apoptosis or dedifferentiation during T2D development. The transcription factor PAX4 is vital for differentiation and survival, thus may be potential enhancer of function islets. Materials & methods: Human cDNA was delivered into human islets an adenoviral vector, effects on were examined. Results: gene delivery significantly improved...

The transcription factor Pax4 plays an essential role in the development of insulin-producing β cells pancreatic islets. Ectopic expression not only promotes cell survival but also induces α-to-β transdifferentiation. This dual functionality makes it appealing therapeutic target for treatment insulin-deficient type 1 diabetes (T1D). In this study, we demonstrated that gene delivery by adenoviral vector, Ad5.Pax4, improved function mouse and human islets promoting islet transdifferentiation,...

Background/Aim: We previously showed that oxaliplatin induces necrotic-like cell death in hepatocarcinomas, and combination with ursodexoycholic acid (UDCA) significantly shifts the to apoptosis. Since mode is crucial on inflammatory responses chemotherapeutic efficacy, mechanism underlying determination of by UDCA was investigated this study. Materials Methods: Apoptosis or necrosis determined apoptotic body formation, caspase-8 activity, LDH release PI inclusion. The involvement lipid...

Abstract Interleukin-17 (IL-17) is a key cytokine in inflammation, which has been shown to play critical roles development of prostate cancer, skin colon and breast cancer. We have previously demonstrated that IL-17 promotes carcinogenesis, accompanied with increased expression matrix metalloproteinase 7 (MMP7) the mouse prostate. The purpose present study was determine whether MMP7 mediates IL-17's action underlying mechanisms. Mmp7 knockout (Mmp7−/−) mice were crossbred phosphatase tensin...

Glucagon-like peptide-1 (GLP-1) inhibits glucagon secretion from a cells and stimulates insulin ß in blood-glucose dependent manner. Whereas the effects of GLP-1 on are mediated by receptor (GLP-1R) has been described detail. The action a-cells, however, is not clear. To determine whether inhibition due to direct effect that occurs through GLP-1R or indirect a-cells stimulation ß-cells, we generated a-cell specific knockout (aGLP-1R KO) mice after expression was verified glucagon-producing...

Abstract Rapidly proliferating cancer cells consume more glycine than rapidly normal cells, which offers an opportunity to target metabolism in the while avoiding causing severe side effects cells. Two-thirds of consumed is synthesized intracellularly, e.g., through conversion serine into by hydroxymethyltransferase (SHMT). Aminomethylphosphonic acid (AMPA, C3H3NO5P) analog glycine, inhibits SHMT enzyme activity, thus blocking glycine. Our previous in-vitro studies have shown that AMPA...

Pax4 is a transcriptional factor which plays critical role in the generation of insulin producing β-cells during embryonic development. Our group previously demonstrated that delivered by adenoviral vector induces expression and reduces glucagon αTC1.9 cells primary human islets. The purpose present study was to determine whether gene pancreatic α-cells become β-cell using lineage tracing techniques confers therapeutic benefits context islet transplantation. In this study, we generated α...