Abstract:
OBJECTIVE:Small cell lung carcinoma (SCLC) expresses phenotypic features of pulmonary neuroendocrine cells and demonstrates a strong etiologic association with smoking. SCLC cell lines express a Raf-1-dependent mitogenic signal transduction pathway, which is thought to transduce the mitogenic signals initiated by neuropeptide autocrine growth factors. Recent studies have identified the tobacco-specific carcinogenic nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as a site-selective high-affinity agonist for the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR), which regulates the growth of a significant subset of SCLC in vitro by stimulating the release of the autocrine growth factor serotonin. The purpose of this study was to identify signaling events initiated by binding of NNK to the alpha7 nAChR. DESIGN:We have used a human SCLC cell line and fetal hamster pulmonary neuroendocrine cells with in vitro kinase activation assays and western blots to assess the levels of expression and activation of Raf-1, MAPK and c-myc to address this issue. RESULTS:Our data show that NNK activates the Raf-1, MAP kinase pathway, resulting in phosphorylation of c-myc. The activation of this signal transduction pathway by NNK was inhibited by the site-selective antagonist for the alpha7 nAChR alpha-bungarotoxin (alpha-BTX) or by the serotonin reuptake inhibitor imipramine, suggesting that the responses to NNK were mediated by nicotinic receptor-initiated release of serotonin. Accordingly, NNK-induced 5-HT release was blocked by alpha-BTX while NNK-induced DNA synthesis was inhibited by alpha-BTX, imipramine, the PKC inhibitor sphingosine or the MEK inhibitor PD98059. SCLC cells demonstrated high basal levels of 5-HT release, DNA synthesis, and over-expressed Raf-1 and MAPK protein suggesting the constitutive activation of an upstream regulator such as the alpha7 nAChR. CONCLUSION:Our findings link, for the first time, the stimulation of a nicotinic acetylcholine receptor by a cancer-causing agent with the activation of a Raf-1/MAPK/c-myc signaling pathway. Furthermore, our data suggest that serotonin uptake inhibitors may protect against the development or be useful in the clinical management of SCLC.
journal_name
J Cancer Res Clin Oncoljournal_title
Journal of cancer research and clinical oncologyauthors
Jull BA,Plummer HK 3rd,Schuller HMdoi
10.1007/s004320100289subject
Has Abstractpub_date
2001-12-01 00:00:00pages
707-17issue
12eissn
0171-5216issn
1432-1335journal_volume
127pub_type
杂志文章abstract:PURPOSE:Interferon alpha (IFNalpha) has been used in the immunotherapy of renal cell carcinoma (RCC), but the various mechanisms of its antiproliferative effects are poorly understood. Recent evidence suggests that IFNalpha is involved in the up-regulation of multidrug resistance (MDR) gene expression, and that the MDR...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s004320050252
更新日期:1999-01-01 00:00:00
abstract::Female wistar rats were fed on an Mg-deficient diet. After 8 to 10 weeks, the thymus glands were strongly degenerated and the number of lymphocytes was reduced, especially in the cortex. Thymus degeneration was associated with a decreased rate of DNA, RNA, and protein biosynthesis and necrosis and phagocytosis of lymp...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00402054
更新日期:1982-01-01 00:00:00
abstract:PURPOSE:We studied the antitumor activity of 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx), which was synthesized by the reactions of 2-amino-5-methylphenol with bovine hemoglobin, on human B cell lymphoblastoid cell lines, P3HR-1 and Raji derived from African Burkitt's lymphoma, and the human T...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-002-0352-3
更新日期:2002-07-01 00:00:00
abstract::Insulin-like growth factor I (IGF-I) exerts pleiotropic effects on mammalian cells via stimulation of its receptor (IGF-IR), a receptor tyrosine kinase. In vivo, IGF-I acts both as a local tissue growth factor and as a circulating hormone. In oncological research, IGF-I has received increased attention as the activate...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
doi:10.1007/s004320050259
更新日期:1999-01-01 00:00:00
abstract::E-cadherin mainly mediated the epithelial cell-cell adhesion, and integrin signaling can modulate the signaling pathway of E-cadherin in the different levels. Up to now, however, it is still unclear that whether E-cadherin could interfere with cell-matrix interaction, a typical adhesion through integrins. In this stud...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-006-0128-2
更新日期:2006-12-01 00:00:00
abstract:PURPOSE:Maintaining telomeres by recruiting telomerase-to-chromosome ends is essential for cancer cell survival. Inhibiting telomerase recruitment to telomeres represents a novel strategy for telomere-based lung cancer therapy. However, approaches for interrupting telomerase recruitment for cancer therapy still need to...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-019-02921-3
更新日期:2019-06-01 00:00:00
abstract::Nosocomial infections caused by COVID-19 will result in the immediate closure of the infected medical facility due to the highly contagious nature of COVID-19, further worsening medical shortages. We performed a Delphi consulting study to develop a risk model based on the experience of recently resumed activities in m...
journal_title:Journal of cancer research and clinical oncology
pub_type: 信件
doi:10.1007/s00432-020-03235-5
更新日期:2020-07-01 00:00:00
abstract:PURPOSE:Human papillomavirus (HPV) type 16 and 18 are the most prevalent genotypes in cervical cancers. The viral oncoproteins E6 and E7 are considered to be tumor-specific targets for immunotherapy. HPV E7 antigen-loaded dendritic cells (DC) were evaluated as cellular tumor vaccine. METHODS:Autologous monocyte-derive...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-003-0462-6
更新日期:2003-09-01 00:00:00
abstract:PURPOSE:Bone morphogenetic proteins (BMPs) are multifunctional regulators of various cell functions. The BMP-signalling network plays a pivotal role during embryogenesis and tumorigenesis. BMPs, e.g. BMP-2 exert their biological function in a time and concentration-dependent manner but also modulated by the context of ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-008-0396-0
更新日期:2008-11-01 00:00:00
abstract::The highly metabolized nitrosourea carmustine (BCNU) is an anticancer agent which alkylates DNA and is metabolized to both active and inactive species by cytochrome P-450 enzymes. Other highly metabolized anticancer drugs have altered toxicities when some histamine H2 antagonists are coadministered. To test this hypot...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00391598
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:The purpose of this study was to characterize changes in the expression of copper-zinc superoxide dismutase (Cu/Zn-SOD) and manganese SOD (Mn-SOD) in oral squamous-cell carcinoma (OSCC). METHODS:Real-time quantitative reverse transcriptase-polymerase chain reaction analysis of Cu/Zn-SOD and Mn-SOD mRNA express...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-009-0610-8
更新日期:2009-11-01 00:00:00
abstract::This special report discusses problems relevant to histological diagnosis of cancer after chemo- and/or radiotherapy. One of the issues relates to pitfalls, i.e. over-, under- or misdiagnosis or oversight, stemming from a lack of concern or awareness of therapeutic effects on tumors or normal tissues. Another set of q...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s004320050269
更新日期:1999-01-01 00:00:00
abstract::In addition to spontaneous uterine endometrial adenocarcinomas at a high incidence (35.1%), development of endometrial hyperplasia/adenoma was also frequently detected in rats of the Donryu strain. The total yield of all observed proliferative endometrial lesions was very high (60.6%). The tumors arose commonly in the...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01637084
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:The aim of our study was to identify factors which influence survival in patients with disseminated seminoma in the good prognostic group according to IGCCCG, as well as to evaluate the impact of treatment intensification in patients with negative prognostic factors. METHODS:We analyzed the database of the pat...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-015-1914-5
更新日期:2015-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:To determine the cytotoxicity of, and radioenhancement by, gemcitabine on a glioma cell line grown as a monolayer and as spheroid cultures. MATERIAL AND METHODS:We used a human glioma cell line, Gli-6, which originated from a biopsy specimen of a patient with a glioblastoma multiforme. Spheroids...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-003-0506-y
更新日期:2004-01-01 00:00:00
abstract::Preoperative cytologic examinations were performed on bronchial material from 92 patients with postsurgical (pathologic) stage I (American Joint Committee) adenocarcinoma of the lung. All patients were followed up for at least 5 years or until death; thus, cases of adenocarcinoma metastatic to the lungs were virtually...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00389247
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:To elucidate the effect of tumor oxygenation status on recovery from damage following gamma-ray or accelerated carbon ion irradiation in vivo, including in quiescent (Q) cells. METHODS:SCC VII tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells. They r...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-009-0552-1
更新日期:2009-08-01 00:00:00
abstract:PURPOSE:To investigate the efficacy and safety of nab-paclitaxel plus S-1 (nab-P/S) versus nab-paclitaxel plus gemcitabine (nab-P/G) as first-line chemotherapy in patients with advanced pancreatic ductal adenocarcinoma (PDAC). METHODS:Treatment-naïve patients with advanced PDAC were equally randomized to receive nab-P...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-020-03442-0
更新日期:2020-11-15 00:00:00
abstract::The purpose of this study was to examine the structure/activity relationships of a series of substituted benzamides as poly(ADP-ribose) polymerase inhibitors. The experimental approach has involved the use of in vitro and in vivo assays in order to gather information either on the intrinsic activity of the benzamides ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01637083
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:In 2008, we reported that 10 Japanese-size cups of green tea daily, supplemented with tablets of green tea extract (GTE), reduced the recurrence of colorectal adenoma by 51.6% in patients after polypectomy. Based on these results, we paid special attention to Japanese cancer patients, who consume green tea ever...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
doi:10.1007/s00432-014-1899-5
更新日期:2015-09-01 00:00:00
abstract::The role of different cytogenetic changes has been extensively evaluated in patients with acute myeloid leukemia (AML), and cytogenetic analysis of AML blasts is essential to form prognostic subgroups in order to stratify for the extent of therapy. Nevertheless, 40-45% of AML patients lack such cytogenetic markers, i....
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
doi:10.1007/s00432-008-0524-x
更新日期:2009-04-01 00:00:00
abstract::Point mutations occurring at codon 201 of the gene coding for the alpha subunit of the stimulatory G protein impair intrinsic GTPase activity and lead to a constitutive activation of adenylate cyclase. We have examined thyroid follicular and papillary carcinomas and follicular adenomas and found samples that bear this...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01366965
更新日期:1995-01-01 00:00:00
abstract::To evaluate the epidermal growth factor receptor (EGFR) protein expression, gene mutations and amplification as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC) receiving gefitinib, we have performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We investig...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-007-0320-z
更新日期:2008-05-01 00:00:00
abstract::Multicellular tumor spheroids (MCTS) grown from the bladder cancer cell line RT112 and from the prostate cancer cell line PCA were exposed to 200 or 800 electromagnetically generated focused ultrasound shock waves. RT112 cells showed a distinct but transient decrease in proliferation whereas the effect of PCA cells wa...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01240146
更新日期:1994-01-01 00:00:00
abstract::This article summarizes the various current uses of cytokines, and bone marrow and peripheral blood stem cell transplantation for cancer treatment. Interferons, interleukin-2 and hematopoietic growth factors are extensively used for the treatment of hematopoietic as well as nonhematopoietic malignancies, either as the...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
doi:10.1007/BF01213315
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:To investigate the levels for some specified microRNAs in human's peripheral blood so as to determine whether they can serve as biomarkers for metastatic non-small-cell lung cancer. METHODS:Use a quantitative stem-loop RT-PCR method to examine the serum levels for certain microRNAs including has-miR-125a-5p, h...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-011-1068-z
更新日期:2012-01-01 00:00:00
abstract::A short-term organ culture of rat tracheal epithelium was used to detect the ability of 53 chemicals to induce UDS. In this system all direct-acting compounds (ultimate or proximate carcinogens) tested induced UDS. Of 24 compounds requiring metabolism (procarcinogens), nine induced UDS, viz., 4NQO, AF-2, BP, DMN, DEN,...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00410663
更新日期:1981-01-01 00:00:00
abstract::The effect of a single blood transfusion on the formation and outgrowth of experimental lung metastases was assessed in two tumor models in rats. The transfusions were given either 1 week before (day -7) or 1 week after (day +7) tumor cell inoculation. The first approach was performed to investigate the effect of tran...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00402776
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:Matrix metalloproteinases (MMPs) are a family of structurally related zinc-dependent endopeptidases that are able to degrade extracellular matrix components. MMPs play a role in tumor invasion and tumor metastasis. MMP-2 (also known as gelatinase A) is expressed in human melanoma cells. METHODS:In this study, ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s004320100257
更新日期:2001-10-01 00:00:00
abstract:PURPOSE:Oxidative stress is considered a risk factor for prostate cancer development and is associated with the production of reactive oxygen species (ROS). The base excision repair gene MYH protects against ROS-mediated damage to DNA. Inherited MYH mutations predispose to colorectal adenomas and cancer. A compromised ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-006-0181-x
更新日期:2007-06-01 00:00:00