Abstract:
:Cholangiocarcinoma is a strongly aggressive malignancy with a very poor prognosis. Effective therapeutic strategies are lacking because molecular mechanisms regulating cholangiocarcinoma cell growth are unknown. Furthermore, experimental in vivo animal models useful to study the pathophysiologic mechanisms of malignant cholangiocytes are lacking. Leptin, the hormone regulating caloric homeostasis, which is increased in obese patients, stimulates the growth of several cancers, such as hepatocellular carcinoma. The aim of this study was to define if leptin stimulates cholangiocarcinoma growth. We determined the expression of leptin receptors in normal and malignant human cholangiocytes. Effects on intrahepatic cholangiocarcinoma (HuH-28) cell proliferation, migration, and apoptosis of the in vitro exposure to leptin, together with the intracellular pathways, were then studied. Moreover, cholangiocarcinoma was experimentally induced in obese fa/fa Zucker rats, a genetically established animal species with faulty leptin receptors, and in their littermates by chronic feeding with thioacetamide, a potent carcinogen. After 24 weeks, the effect of leptin on cholangiocarcinoma development and growth was assessed. Normal and malignant human cholangiocytes express leptin receptors. Leptin increased the proliferation and the metastatic potential of cholangiocarcinoma cells in vitro through a signal transducers and activators of transcription 3-dependent activation of extracellular signal-regulated kinase 1/2. Leptin increased the growth and migration, and was antiapoptotic for cholangiocarcinoma cells. Moreover, the loss of leptin function reduced the development and the growth of cholangiocarcinoma. The experimental carcinogenesis model induced by thioacetamide administration is a valid and reproducible method to study cholangiocarcinoma pathobiology. Modulation of the leptin-mediated signal could be considered a valid tool for the prevention and treatment of cholangiocarcinoma.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Fava G,Alpini G,Rychlicki C,Saccomanno S,DeMorrow S,Trozzi L,Candelaresi C,Venter J,Di Sario A,Marzioni M,Bearzi I,Glaser S,Alvaro D,Marucci L,Francis H,Svegliati-Baroni G,Benedetti Adoi
10.1158/0008-5472.CAN-07-6682subject
Has Abstractpub_date
2008-08-15 00:00:00pages
6752-61issue
16eissn
0008-5472issn
1538-7445pii
68/16/6752journal_volume
68pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::The Ral family of small G proteins has been implicated in tumorigenesis, invasion, and metastasis. However, little emphasis has been placed on clarifying the individual roles of the two Ral proteins, RalA and RalB, in these processes in view of their high sequence homology. Here we analyze the separate contributions o...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-1957
更新日期:2005-08-15 00:00:00
abstract::The protein phosphatase 2 (PP2A) holoenzyme consists of a catalytic subunit, a scaffold subunit, and a regulatory subunit. Based on loss-of-function analysis using PP2A catalytic inhibitors or inhibition via tumor viral antigens, limited studies suggest that PP2A is a putative tumor suppressor. However, PP2A has also ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-2119
更新日期:2016-04-15 00:00:00
abstract::Pristane (2,6,10,14-tetramethylpentadecane) is a C19-isoalkane that promotes the development of plasmacytomas in genetically susceptible BALB/c mice. Similarities between the effects of pristane and protein kinase C (PKC)-activating phorbol esters suggested that the tumor promoting activity of pristane might involve t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::Ultrastructural studies of the effects of adriamycin on liver and cardiac cell nucleoli of the rat showed that nucleolar segregation occurred within 1 hr after an i.v. injection of a 40-mg/kg dose. Between 3 and 27 hr after this single dose, liver cell nucleoli progressively reverted to a normal ultrastructure. Nucleo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-05-01 00:00:00
abstract::SNAI2 overexpression appears to be associated with poor prognosis in breast cancer, yet it remains unclear in which breast cancer subtypes this occurs. Here we show that excess SNAI2 is associated with a poor prognosis of luminal B HER2+/ERBB2+ breast cancers in which SNAI2 expression in the stroma but not the epithel...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-0278
更新日期:2020-12-01 00:00:00
abstract::cis-Bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (NDDP), a lipophilic cisplatin analogue containing two branched leaving groups of 10 carbon atoms, is undergoing clinical evaluation in a liposomal formulation. In previous studies, NDDP entrapped in multilamellar vesicles composed of dimyristoylphosp...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-11-15 00:00:00
abstract::Previous work in our laboratory has indicated that free fatty acids stimulate synthesis of fibrinogen by the liver. The effect of the hypolipidemic agent clofibrate on hyperfibrinogenemia associated with tumors was evaluated by monitoring clofibrate-induced changes in plasma fibrinogen concentration and biosynthesis o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-10-01 00:00:00
abstract::Malignant changes are often accompanied by alterations in activity and composition of the plasminogen activators (PA). To study the relationship between PA expression and the development of colorectal cancer, we determined urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) activit...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-09-01 00:00:00
abstract::Carcinogenic heterocyclic amines are activated by N-acetyltransferase (NAT) enzymes, encoded by NAT1 and NAT2, to genotoxic compounds that can form DNA adducts in the colon epithelium. We have examined the relation of polymorphisms in the genes coding for both enzymes to risk of colorectal cancer and the gene-environm...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::We investigated the relationship between DNA cytosine methylation and the expression of two genes associated with resistance to DNA methylation damage. Variants of RajiMex- cells acquired resistance to N-methyl-N-nitrosourea by either reactivating a previously silent O6-methylguanine-DNA methyltransferase (MGMT) gene ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-06-15 00:00:00
abstract::Hepsulfam (NSC 329680, 1,7-heptanediol disulfamate) is an alkylating agent that showed excellent activity against mouse and human mammary carcinoma in preclinical studies. We therefore studied the cytotoxicity of this drug in six human breast cancer cell lines (AdrRMCF7, WTMCF7, Hs578T, MDA-MB-231, T47D, and MDA-MB-46...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-03-15 00:00:00
abstract::The influence of phorbol diesters on the in vitro hydrolysis of diacylglycerols was examined using enzymes from rat serum, porcine pancreas, and Rhizopus delemar. Two main phenomena were observed: 12-O-tetradecanoylphorbol-13-acetate (TPA), when added to the enzyme assay system, stimulated 2- to 3-fold the hydrolysis ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::Splenocytes from mice bearing a cachexia-inducing tumor (MAC16) have been fused with mouse myeloma cells to produce hybridomas, which have been cloned to produce antibody reactive to a material which copurified with a lipid-mobilizing factor isolated from the same tumor. The monoclonal antibody has been used to invest...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-03-15 00:00:00
abstract::A nationwide study of all 3183 female patients with breast cancer in Israel diagnosed over a 7-year period (1960 to 1966) was conducted. Monthly series analysis showed a clear seasonal pattern in the symptomatology of the disease most pronounced in patients younger than 55 years, in all ethnic groups, mainly confined ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-02-01 00:00:00
abstract::The characteristics of EMT6 tumors in young adult (3- to 4-month-old) and aged (20- to 28-month-old) BALB/c KaRw mice were compared. The number of tumor cells implanted s.c. necessary to cause tumors in 50% of the injection sites was lower in aging than in young adult mice (69 and 138 cells for young adult mice versus...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-02-01 00:00:00
abstract::We have examined the ability of ingenol to bind to and activate protein kinase C and to induce similar responses to the phorbol esters in biological systems. The rationale was that ingenol possesses the critical functionalities of the phorbol ester pharmacophore with the exception of the hydrophobic domain; it might t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::RAF kinase inhibitor protein (RKIP) is a seminal regulator of intracellular signaling and exhibits both antimetastatic and antitumorigenic properties. Decreased expression of RKIP has been described in several human malignancies, including acute myelogenous leukemia (AML). As the mechanisms leading to RKIP loss in AML...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-3049
更新日期:2016-06-15 00:00:00
abstract::The environmental contaminant 6-nitrochrysene (6-NC) has been shown to induce adenomas and adenocarcinomas in the colons of rats. The present study aimed at providing a better understanding of mechanisms that are responsible for this effect. Three female CD rats were injected i.p. with [3,4,9,10-3H]6-NC [9 mumol/rat (...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::The BCR/ABL fusion protein is a constitutively active tyrosine kinase that is responsible for the pathogenesis of chronic myelogenous leukemia (CML). Clinically, CML is characterized by a chronic phase (CP) that eventually terminates into a blast crisis (BC). BC transformation is associated with accumulation of CD34+ ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00
abstract::Multiple copies of N-myc proto-oncogene are only rarely detected in localized neuroblastomas (NBs), and the prognostic relevance of amplification in this subset of patients is not clear. We analyzed a series of 850 children with NB admitted to a Pediatric Oncology Group NB Biology Study and identified six patients wit...
journal_title:Cancer research
pub_type: 杂志文章,多中心研究
doi:
更新日期:1995-02-15 00:00:00
abstract::We reported recently that medium conditioned with mouse lung microvessel endothelial cells possessed chemotactic activity for a highly lung-metastatic variant (L17) of the RAW117 murine large-cell lymphoma cell line but not for the poorly metastatic parental cells (P) or a liver-metastasizing variant (H10). The chemot...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract::Proline is a readily released stress substrate that can be metabolized by proline oxidase (POX) to generate either reactive oxygen species (ROS) to induce apoptosis or autophagy or ATP during times of nutrient stress. However, the contribution of proline metabolism to tumorigenesis in hypoxic microenvironments has not...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-0080
更新日期:2012-07-15 00:00:00
abstract::A cascade of events leading to hypertrophy has been proposed and implicated in growth regulation in a variety of normal and neoplastic cells and tissues. There is a tightly coupled temporal sequence: (a) cyclic adenosine 3':5'-monophosphate-dependent protein kinase (cAPK) activation; (b) ornithine decarboxylase (ODC) ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-12-01 00:00:00
abstract::Ovarian and testicular tumors were induced in the offspring (F1 generation) of MRC rats that received single or multiple doses of N-nitrosobis(2-oxopropyl)amine on the 14th, 18th, and/or 20th days of pregnancy. The ovarian tumor incidence was significantly higher (46%) in the F1 generation exposed to the carcinogen a ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-08-01 00:00:00
abstract::Although androgen ablation therapy is effective in treating primary prostate cancers, a significant number of patients develop incurable castration-resistant disease. Recent studies have suggested a potential synergy between vaccination and androgen ablation, yet the enhanced T-cell function is transient. Using a defi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-2499
更新日期:2012-04-15 00:00:00
abstract::Male Sprague-Dawley rats were given weekly s.c. injections of 1,2-dimethylhydrazine (21 mg/kg) for 20 weeks. The injections were then discontinued, and, after an interval of 2 to 8 weeks, experimental animals were given i.p. injections of 5,6-dihydroxytryptamine (5,6DHT) at a dose of 40 mg/kg and sacrificed at interva...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-04-01 00:00:00
abstract::Glutamine supplementation has been advocated for patients requiring parenteral nutritional support. However, the direct effect of glutamine on neoplastic cells is poorly understood. We therefore investigated the effects of glutamine on the proliferation, differentiation, and cell-matrix interactions of two human colon...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-11-15 00:00:00
abstract::DNA methyltransferase 1 (DNMT1)-deficient mice are tumor-prone, and this has been proposed to result from the induction of genomic instability. To address whether loss of DNMT1, or the related protein DNMT3b, results in genomic instability in human cancer cells, we used a near-diploid human colorectal cancer cell line...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1961
更新日期:2005-10-01 00:00:00
abstract::Murine sarcoma virus (Moloney strain) (MSV-M)-induced tumors are unusual in that they regularly appear less than 2 weeks after virus inoculation, progress for 1 to 2 weeks, and are rejected by normal adult BALB/c mice. Rejectio leaves the animals immune to tumor induction. In the present study, presensitization of nor...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-12-01 00:00:00
abstract::Studies of V79-171 cells were undertaken to determine what extracellular or intracellular derivative of the drug WR-2721 is associated with radioprotection. The effect of preincubation at 23 +/- 1 degree C with WR-2721, and with derivatives of WR-2721 produced in medium containing alkaline phosphatase, upon survival o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00