Abstract:
:Nicotinic acetylcholine receptors (nAChR) are expressed on bronchial epithelial and non-small cell lung cancer cells and are involved in cell growth regulation. Nicotine (classical nAChR agonist) induced cell proliferation, whereas nAChR antagonists, d- tubocurarine or alpha-cobratoxin (alpha-CbT), induced cell death. In the current study, we further explored the antitumor potential mechanisms and activities of alpha-CbT. NOD/SCID mice were grafted intraperitoneally or orthotopically and treated with alpha-CbT. alpha-CbT treatment [0.04 ng/kg or 0.12 ng/kg] induced a strong reduction in tumor size ( approximately 90%) in comparison with mice treated with the vehicle alone. Tumor inhibition was related to severe induction of apoptosis. Moreover, neoangiogenesis was strongly inhibited (reduction of cells positive to vascular endothelial growth factor and CD31). Biochemical analyses of the cells, isolated by the primary lung tumor in alpha-CbT-treated mice, showed apoptosis features characterized by: (i) inhibition of BAD phosphorylation at Ser(112) and Ser(136); (ii) BAD dissociation from 14-3-3; (iii) BAD association with BCL-XL; and (iv) cleavage of caspase-9. Moreover, these cells were unable to grow in soft agar and develop tumor, when reinjected into mice. The small interfering RNA-mediated silencing of the alpha7-nAChR gene confirmed that alpha-CbT specifically inhibited the alpha7-nAChR-mediated survival pathway in A549 cells. Furthermore, the specificity of alpha-CbT is reinforced by the lack of effect of short chain toxin (Erabutoxin-a). Once more, the no effect of the low-affinity R33E-modified alpha-CbT strengthened the specificity of this inhibition. Although alpha7-nAChR antagonists, such as alpha-CbT, are unlikely to be a primary therapy, it may provide lead compounds for the design of clinically useful drugs.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Paleari L,Sessa F,Catassi A,Servent D,Mourier G,Doria-Miglietta G,Ognio E,Cilli M,Dominioni L,Paolucci M,Calcaterra A,Cesario A,Margaritora S,Granone P,Russo Pdoi
10.1002/ijc.24299subject
Has Abstractpub_date
2009-07-01 00:00:00pages
199-211issue
1eissn
0020-7136issn
1097-0215journal_volume
125pub_type
杂志文章abstract::Differentiated thyroid carcinoma (TC) is threefold more common in women than in men and, therefore, a role of female hormones in the etiology of differentiated TC has been suggested. We assessed these hypotheses in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 345,157 women (mea...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29067
更新日期:2015-03-01 00:00:00
abstract::BALB/c peritoneal plasmacytomas induced by a variety of agents are invariably associated with a c-myc translocation. In contrast, naturally arising bone marrow plasma cell tumors in C57BL/KaLwRij mice lack this translocation. This difference has led to the suggestion that these are 2 fundamentally different plasma cel...
journal_title:International journal of cancer
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doi:10.1002/(sici)1097-0215(19970904)72:5<892::aid-ijc
更新日期:1997-09-04 00:00:00
abstract::To identify molecular markers for the progression of head-and-neck squamous cell carcinoma (HNSCC), we used RNA arbitrarily primed (RAP) PCR to determine the qualitative and quantitative differences in gene expression between normal epithelial cells, those derived from dysplastic oral mucosa and invasive and metastati...
journal_title:International journal of cancer
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doi:10.1002/ijc.10403
更新日期:2002-06-01 00:00:00
abstract::Extranodal, nasal NK/T-cell lymphomas are regularly Epstein-Barr virus (EBV)-positive, with a type II latency pattern, expressing thus EBNA-1 and LMP1. The contribution of EBV to the tumor development is not known. Similarly to normal natural killer (NK) cells, cell lines derived from malignancies with a NK phenotype ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.22139
更新日期:2006-12-15 00:00:00
abstract::The water-soluble scavengers ascorbic acid (Asc), cysteine (Cys), glutathione (GSH) and uric acid (UA) as well as DNA content were determined in 40 breast tissue samples (neoplastic and non-neoplastic tissues from 20 patients). To allow proper homogenization to take place, a fixed number of sections was cut from a tis...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910410509
更新日期:1988-05-15 00:00:00
abstract::Genome-wide association studies (GWAS) have identified several loci contributing to lung cancer and COPD risk independently; however, inflammation-related pathways likely harbor additional lung cancer risk-associated variants in biologically relevant immune genes that differ dependent on COPD. We selected single nucle...
journal_title:International journal of cancer
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abstract::Monoclonal antibodies (MAbs) reactive with the ganglioside fucosyl GM1 (Fuc-GM1), an antigen associated with small-cell carcinoma of the lung (SCLC), were tested for their ability to mediate tumor-cell killing in vitro in conjunction with humoral and cellular effectors and to inhibit tumor engraftment in nude mice in ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910490619
更新日期:1991-12-02 00:00:00
abstract::A case-control study of prostate cancer (PC) was undertaken in Athens, Greece. Cases were 320 patients with histologically confirmed incident disease, whereas controls were 246 patients without history or symptomatology of benign prostatic hyperplasia, treated in the same hospitals as the cases for minor diseases or c...
journal_title:International journal of cancer
pub_type: 杂志文章,多中心研究
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更新日期:1999-03-01 00:00:00
abstract::Syrian-hamster-derived lymphotoxin inhibits benzo(a)pyrene and ultraviolet carcinogen-induced in vitro morphologic transformation of diploid secondary passage hamster embryo cells. When lymphotoxin is added up to 4 days post carcinogen, the reduction in the frequency of morphologic transformation 6 days after carcinog...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910270108
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abstract::To facilitate the use of multileaf collimator (MLC) in field shaping, we tested the hypothesis that the changes in the penumbra due to MLC replacing a Cerrobend block can be related to a change in the margin of the block. We also investigated if it is possible to estimate the effect of MLC replacing a block in terms o...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.1038
更新日期:2001-12-20 00:00:00
abstract::Natural killer (NK)6 cell activity of peripheral blood lymphocytes against human leukemia cell lines was measured in patients with chronic B-cell lymphocytic leukemia (CLL) and age- and sex-matched controls. In order to remove the leukemia cells that interfere with the in vitro assay we (1) isolated lymphocytes that f...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910270310
更新日期:1981-03-15 00:00:00
abstract::The calcium-sensing receptor (CaSR) is suggested to mediate the antiproliferative effects of calcium in colon. However, in colorectal cancer (CRC) the expression of the CaSR is silenced and the underlying mechanisms leading to its loss are poorly understood. We investigated whether loss of the CaSR expression in color...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.28856
更新日期:2014-11-01 00:00:00
abstract::Rabbits were immunized with extracts of primary or grafted intestinal adeno-carcinomas induced by carcinogenic drugs in inbred rats. After absorption with normal tissue extracts, the antisera were able to recognize three tumor-associated antigens. Two of them were glycoproteins, present in cancer cells but also, in tr...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910150117
更新日期:1975-01-15 00:00:00
abstract::CD43 is a leukocyte-associated sialoglycoprotein which is also expressed in human colon adenoma and carcinoma. To obtain monoclonal antibodies (MAbs) that would react with CD43 in a glycosylation-independent way, antibodies were raised against a peptide corresponding to a portion of the CD43 cytoplasmic domain. Hybrid...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19990702)82:1<52::aid-ijc1
更新日期:1999-07-02 00:00:00
abstract::An immunopotentiating factor associated with spleen cells of C57BL/6J mice bearing the 3LL tumor is described. Supernatants of cultured spleen cells from tumor-bearing mice (TBM) augmented the generation of both 19S and 7S antibody-producing cells, when injected with sheep erythrocytes into syngeneic C57BL/6J mice. Th...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910220416
更新日期:1978-10-15 00:00:00
abstract::BW 5147 lymphoma cells are non-invasive tumor cells which do not generate experimental metastases following i.v. inoculation. In contrast, s.c. and intra-splenic (i.s.) growth of BW cells resulted in widespread colonization of liver and spleen. Cells derived from either s.c. tumors or metastatic lesions did generate m...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910410514
更新日期:1988-05-15 00:00:00
abstract::We undertook a study to determine the role and regulation of expression of urokinase-type plasminogen activator in squamous-cell carcinoma of the oral cavity. The contribution of urokinase to the invasive process was clearly demonstrated in experiments in which in vitro invasion by a cultured squamous-cell carcinoma c...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910540113
更新日期:1993-04-22 00:00:00
abstract::Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit proliferation and angiogenesis in colorectal cancer. We examined a possible involvement of store-operated calcium (SOC) entry in human colon carcinoma cells (HRT-18), which require calcium for proliferation. Acetyl-salicylic-acid (ASA), mefenamic acid (MEF) and su...
journal_title:International journal of cancer
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更新日期:2001-06-15 00:00:00
abstract::We describe an innovative strategy to quantify risk of cancer associated with varying levels of exposure to chronic parasitic infection through the identification of asymptomatic cases of cholangiocarcinoma within a population-based survey of Opisthorchis viverrini infection. Stool samples from 12,311 adults over age ...
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更新日期:1994-11-15 00:00:00
abstract::G-banding analyses of 14 independently derived B-cell lymphomas showed the frequent occurrence of chromosome 15 trisomy. It was present in seven of nine spontaneous B-cell lymphomas, but in company with other trisomies, monosomies and marker chromosomes. In five carcinogen-induced primary B-cell leukemias, trisomy 15 ...
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abstract::Immune cells in tumor microenvironment play a prominent role in tumor progression and metastasis. MicroRNA-155 (miR-155) represents an important player in innate and adaptive immunity by regulating differentiation, maturation and activation of macrophages, dendritic cells, B cells and T cells. However, the role of miR...
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journal_title:International journal of cancer
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更新日期:2003-01-01 00:00:00
abstract::IL-15 is an immunostimulatory cytokine with IL-2-like activities. To exploit the potential role of IL-15 in cancer immuno-/gene therapy, we engineered murine TS/A cells with different IL-15 cDNA constructs. Significant IL-15 secretion was achieved only by the use of a modified cDNA encoding for an IL-15 pre-protein be...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:
更新日期:2000-08-15 00:00:00
abstract::Studies of colon cancer risk in males have reported strong positive associations with obesity, particularly with central adiposity. The association has been weaker and less consistent for women. In a prospective cohort study of women, body measurements were taken directly; fat mass and fat-free mass being estimated by...
journal_title:International journal of cancer
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journal_title:International journal of cancer
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abstract::Although the incidence of, and deaths due to, malignant melanoma are rising at a rapid rate, few experimental models mimic the highly metastatic properties associated with the pathogenesis of the human disease, making study of the disease difficult. Thus, new human models are required to understand melanoma biology, e...
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