Дисертації з теми "Lung carcinomas"
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Xinarianos, George. "Genetic alterations in non-small cell lung carcinomas." Thesis, University of Liverpool, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343688.
Повний текст джерелаKim, Young. "The Effects of Tarsh Overexpression on Lung Carcinomas." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/498.
Повний текст джерелаMerikallio, H. (Heta). "Claudins and epitheliomesenchymal transition in lung carcinomas and chronic obstructive pulmonary disease." Doctoral thesis, Oulun yliopisto, 2013. http://urn.fi/urn:isbn:9789526202471.
Повний текст джерелаTiivistelmä Keuhkosyöpä ja keuhkoahtaumatauti ovat yleisiä tupakoinnin aiheuttamia keuhkosairauksia, joissa on korkea kuolleisuus. Tupakointi aiheuttaa muutoksia keuhkojen epiteelisoluissa ja solujen välisissä liitoksissa. Tiivisliitokset solujen välillä säätelevät epiteelin rakennetta ja läpäisevyyttä. Klaudiinit ovat proteiineja, jotka muodostavat tiivisliitoksen yhdessä okkludiinin kanssa. Tiivisliitos proteiinien toimintahäiriöt voivat johtaa solujen välisten liitosten katoamiseen ja epiteelin hajoamiseen sekä epiteelisolujen muuntumiseen mesenkymaalisten solujan kaltaisiksi. Nämä seikat lisäävät invaasiota keuhkosyövissä ja saattavat altistaa pahenemisvaiheisiin keuhkoahtaumataudissa. Väitöskirjassa tutkittiin klaudiinien ilmentymistä ja säätelyä keuhkosyövässä ja keuhkoahtaumataudissa. Klaudiinien1, 2, 3, 4, 5 ja 7 esiintyminen keuhkosyövän histologisissa alatyypeissä vaihteli. Klaudiinien 1, 4 ja 7 voimakas ilmentyminen voitiin yhdistää pidempään elinikään potilailla, joilla oli levyepiteeli- tai adenokarsinooma. Klaudiini 3:n ilmentyminen liittyi keuhkoahtaumatautiin suurissa hengitysteissä. Klaudiinien 3 ja 4 voimakas ilmeneminen pienissä ilmateissä oli yleisempää keuhkoahtaumatautipotilailla ja tupakoitsijoilla kuin tupakoimattomilla henkilöillä. Transkriptiotekijä snailin puuttuminen keuhkosyövässä liittyi potilaiden pidempään elinaikaan. Klaudiinien 5 ja 7 ilmeneminen oli voimakkaampaa, kun snailin määrä oli vähäinen. Klaudiinien 1 ja 3 ilmeneminen väheni snail:in ollessa voimakas keuhkosyövässä. Traskriptiotekijöiden (slug ja twist) ilmeneminen liittyi käänteisesti klaudiinien ilmentymiseen pienissä ja suurissa ilmateissä. Slugin ilmeneminen oli voimakkaampaa tupakoimattomilla henkilöillä kuin tupakoivilla tai keuhkoahtaumatautia sairastavilla. Transkriptiotekijöiden snail, slug ja twist toiminnan estäminen lisäsi klaudiinien määrää normaaleissa keuhkon epiteelisoluissa. Poikkeuksen muodostivat klaudiinit 2 ja 7, joiden määrä väheni kun snail:in toiminta oli estetty. Adenokarsinooma-soluissa snailin estolla ei ollut vaikutusta, ja levyepiteelisyövän soluissa klaudiinien 3, 4 ja 7 määrä kasvoi. Snail myös vähensi solujen invaasiota. Transkriptiotekijä twistin toiminnan esto normaaleissa keuhkoepiteelisoluissa nosti solumaton läpi kulkevan sähkön resistenssiä, mikä on osoitus tiiviistä solujen välisistä liitoksista
Vieira, Thibault. "Caractérisation des carcinomes sarcomatoïdes primitifs pulmonaires." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066552/document.
Повний текст джерелаSarcomatoid carcinomas are a rare subtype of non-small cell lung cancer (NSCLC). Prognostic seems less favourable than other subtypes of NSCLC. Our team works to determine molecular characteristics of these tumors. In this work, we demonstrated that sarcomatoid carcinomas are chemoresistant to platinum based regimen in vitro and in vivo (primary cell lines) compared to other NSCLC. We demonstrated that this tumors share immunohistchemical, moleculary similarities with NSCLC validating the WHO classification. It is possible that these tumors came from cancer stem cell or underwent an epithelial-mesenchymal transition. Specificities of this transition remained undefined. Moreover these tumors presented a lot of molecular alterations allowing to investigate targeted therapies such as MET inhibitors. At last, we shows the implication of the immune system, the strong infiltration of TCD8+ lymphcoytes CD163+ macrophages and the expression of PD-L1, allowing to hope new perspective of research, innovative treatment
Blat, Irene Catherine. "Functional miRNA regulation of metastatic genes promotes tumor cell dissemination in non-small cell and small cell lung carcinomas." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/80982.
Повний текст джерелаCataloged from PDF version of thesis. Vita.
Includes bibliographical references.
Tumor progression, from initiation to advanced metastatic disease, requires the orchestration of a diverse group of cell-intrinsic and extrinsic factors. This multifactorial disease is promoted by an accumulation of genetic and epigenetic changes that confer selective advantage to cells and enable unrestrained proliferation, survival, motility, and self-renewal. While much emphasis over the last 35 years has been dedicated to understanding the regulators of tumor initiation, the number of cancer-related deaths worldwide continues to rise, of which the majority are attributed to metastasis. The lengthy progression to metastasis requires invasion out of the primary tumor site and into the bloodstream, survival in and exit from circulation, and colonization and expansion in a foreign environment. Developmental pathways such as the Transforming Growth Factor [beta] (TGF[beta]) signaling network are frequently dysregulated during metastatic progression due to the similarities between early embryogenesis and tumor progression. Furthermore, the TGF[beta] pathway highlights how cell-intrinsic and extrinsic signals help coordinate the complex interactions required between tumor cells, as well as those of the tumor microenvironment to achieve metastasis. Facilitating alterations to pathways such as TGF[beta] and many others are modulators of gene expression that can target multiple nodes of the signaling cascade instead of requiring genetic alterations to single genes. Moreover, in the last decade, emphasis on the role of noncoding RNAs in post-transcriptional modifications has revealed their important contribution in the regulation of developmental programs across metazoan species. More recently, the role of alterations in expression of small noncoding RNAs, microRNAs (miRNAs) has emerged as a significant contributor to disease states, including each stage of tumor progression from initiation to metastatic colonization. miRNAs hold great promise not only as biomarkers but also as potential therapeutics. For these reasons, we have characterized the role of two important examples of miRNA families - the miRNA-200 family and the miRNA-1 7~92 cluster - that regulate early stages of tumor initiation in addition to later steps of cell migration, invasion, survival, and colonization. Examination of their contribution to tumor progression in relevant in vitro and in vivo cellular contexts using genetic tools reveals they are functional contributors to tumor cell dissemination. Furthermore, modulation of their expression in the appropriate tumor microenvironments elucidates a network of targets underlying the molecular mechanisms of metastasis.
by Irene Catherine Blat.
Ph.D.
Gonterman, Ryan M. "Parathyroid hormone-related protein gene expression and function relationship with oncogenic pathways in the skin and squamous cell carcinomas of the lung /." [Bloomington, Ind.] : Indiana University, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3324517.
Повний текст джерелаTitle from PDF t.p. (viewed on May 13, 2009). Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4693. Adviser: John G. Foley.
Zschaeck, Sebastian, Monique Simon, Steffen Löck, Esther G. C. Troost, Kristin Stützer, Patrick Wohlfahrt, Steffen Appold, et al. "PRONTOX – proton therapy to reduce acute normal tissue toxicity in locally advanced non-small-cell lung carcinomas (NSCLC): study protocol for a randomised controlled trial." BioMed Central, 2016. https://tud.qucosa.de/id/qucosa%3A30184.
Повний текст джерелаZschaeck, Sebastian, Monique Simon, Steffen Löck, Esther G. C. Troost, Kristin Stützer, Patrick Wohlfahrt, Steffen Appold, et al. "PRONTOX – proton therapy to reduce acute normal tissue toxicity in locally advanced non-small-cell lung carcinomas (NSCLC): study protocol for a randomised controlled trial." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-219714.
Повний текст джерелаRangel, Maristela Peres. "Relevância dos proteoglicanos como biomarcadores prognósticos e preditivos em carcinomas não-pequenas células e seu impacto na carcinogênese pulmonar." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5144/tde-01032017-140343/.
Повний текст джерелаIntroduction. The relationship between the extracellular matrix (ECM) components and cancer cells have an important role on cancer development and progression. Between the most important molecules present on the ECM are the glycosaminoglycans and their respective proteoglycans. Studies have reported that they have different behaviours when in the presence of malignant tissues and influence the development of breast, pancreas and colon cancers. Likewise, proteins as solCD44 and cofilin-1 also have shown direct influence in tumor progression. Regarding that, there is growing interest among scientists in analyzing the expression of these molecules in body fluids as a screening tool of high risk patients and as a diagnostic and prognostic lung cancer biomarker. Objectives. The aims of this study were to recognize the impact of hyaluronan and the proteoglycans (biglycan, glypican, perlecan, syndecan e versican) on lung cancer carcinogenesis as well as its impact on patient\'s survival; verify if the solCD44 e cofilina-1 concentrations in the sputum of lung cancer patients could distinguish them from patients with COPD and healthy volunteers. Results. A direct association was found between tumors expressing high amounts of hyaluronan and CD34 in tumoral stroma. Heparan and chondroitin sulphate concentrations were higher in tumor specimens when compared to normal lung tissue. All proteoglycans, in exception of syndecan, showed a lower expression in tumoral tissue and biglycan and versican showed association with the clinical pathological features. Protein expression of biglycan, perlecan and versican was higher in the normal tissue when compared to stroma and tumoral cells. COX regression controlled by age, histological types and gene expression of biglycan, syndecan e glypican demonstrated that female patients had higher survival rates with high gene expression of perlecan and the patients with T1 stage, lack of linfonode Maristela Peres Rangel Tese de doutorado - USP metastasis and gene expression of versican had lower risk of death. Cofilin-1 concentration was higher in the sputum of lung cancer patients when compared to a high risk group and healthy volunteers. Also, the solCD44 concentration was higher in the sputum of lung cancer patients when compared to a high risk group and healthy volunteers. ROC cruve analysis demonstrated that sputum cofilin-1 was capable to distinguish high risk patients from lung cancer patients with na area under the curve of 0.69 and with a cut off at 802.5 pg/mL the curve presented 60% de sensitivity and 54% specificity. Sputum solCD44 was also capable to distinguish high risk patients from lung cancer patients with na area under the curve of 0.67 and with a cut off at 65.8 pg/mL the curve presented 50% de sensitivity and 84% specificity. Conclusions. Hyaluronan expression showed a correlation with tumoral growth through angiogenesis processes. The biomolecular analysis demonstrated that matrix proteoglycans are potencial lung cancer prognostic biomarkers. Sputum analyses showed that solCD44 and cofilin-1 are potencial molecules in lung cancer detection
Rangel, Maristela Peres. "Relevância clínica da concentração do ácido hialurônico no escarro e em espécimes tumorais de pacientes portadores de carcinomas de pulmão." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-25102012-162649/.
Повний текст джерелаIntroduction. Hyaluronan is an extracellular matrix non-sulfated glycosaminoglycan. Some have reported that its abnormal production and degradation can influence the behaviour of different types of tumours like breast, prostate, bladder and lung cancer. Therefore, hyaluronan quantitative analysis in tissues and body fluids like blood, urine and sputum has shown promise on the high risk patients screening and as diagnostic/prognostic marker of some diseases. Objectives. Verify if there are differences in the levels of hyaluronan in tumoral and non-tumoral lung cancer specimens, as well as its impact on the patients survival; verify if sputum samples present the same differences; verify the role of hyaluronan quantitative analysis in the screening of lung cancer patients between patients with chronic obstructive pulmonary disease and healthy volunteers. Results. Lung cancer tumoral specimens showed higher levels of hyaluronan when compared to non-tumoral specimens even when the specimens were histologically categorized. There was no correlation between hyaluronan levels and the patients clinical features, however, an impact in the patients survival was observed: patients with tumoral hyaluronan levels > 364,36 g/g had a lower survival rate than patients with < 364,36 ug/g. We have shown that lung cancer patients show an elevated production of hyaluronan in the sputum. This characteristic was independent of the clinical features but dependent of the histologic type. The hyaluronan quantitative analysis for the screening of lung cancer patients between healthy volunteers showed a sensitivity of 87% for hyaluronan levels >11,13ng/mg in the sputum. In this group levels > 31,44ng/mg showed 100% specificity and 51% sensibility. On a second group (lung cancer patients vs chronic obstructive pulmonary disease patients) levels of sputum hyaluronan > 48,36ng/mg showed 100% specificity to exclude chronic obstructive pulmonary disease patients from lung cancer patients. The sensibility for this cut-off point was 33%. Conclusion. Hyaluronan quantitative analysis in the tissues is a promising lung cancer prognostic marker considering the differences between hyaluronan levels on tumoral and nontumoral tissues. Not only this, but, the differences observed in the tissues were observed in the sputum as well. Hence, the hyaluronan quantitative analysis is a promising strategy in the screening of high risk individuals that might develop lung cancer
Rêgo, Juliana Florinda de Mendonça. "Análise e comparação da expressão imunoistoquímica de marcadores moleculares (ERCC1, Bcl-2, Lin28a e Ki67) potencialmente preditores de resposta à quimioterapia em carcinomas neuroendócrinos extra-pulmonares e carcinoma de pequenas células de pulmão." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-06022017-155301/.
Повний текст джерелаINTRODUCTION: Small cell lung cancer (SCLC) and high-grade extrapulmonary neuroendocrine carcinomas (EPNEC) share similar histopathological features and treatment, but outcomes may differ. We evaluated the expression of biomarkers and their association with response rate (RR) to platin-based chemotherapy and overall survival (OS) in these entities. METHODS: We conducted a retrospective analysis of patients with advanced EPNEC and SCLC treated with platinum-based chemotherapy. A single pathologist (R.S.S.M.) revised all samples. Paraffin-embedded tumor samples were tested for Ki-67, ERCC1, Bcl-2 and Lin28a expression by immunohistochemistry (IHC). Final IHC score (H-score) was calculated multiplying the intensity of staining by grading (0-300, with >= 200 considered positive). Biomarkers were analyzed as both categorical and continuous variables. RR was determined by RECIST 1.1. Associations between each biomarkers expression and RR were assessed using Chi-square or Fisher\'s exact test for categorical variables and univariate logistic regression for continuous variables. OS was estimated by the Kaplan-Meier method and curves were compared by log-rank. Cox regression analysis was used to evaluate any association between biomarkers expression (continuous variables) and OS. RESULTS: From July 2006 to July 2014, 142 patients were identified: N=82 (57,7%) with SCLC and N=60 (42,3%) with EPNEC. Baseline clinical characteristics were similar. Median Ki67 was 60% (7-100) among SCLC patients and 50% (20-95%) in EPNEC (p=0,858). With a median of 5 cycles per patient in both groups (N=123 evaluable patients), the RR was significantly higher in the SCLC group (86,8% vs 44.6%; p < 0.001). Median OS (N=132 evaluable patients) was similar between the groups (10.3 months in SCLC and 11.1 months in EPNEC; p=0,069). In the EPNEC group, there wasn\'t any difference in OS or RR between the patients with welldifferentiated (N=13) and poorly differentiated carcinoma (N=47). ERCC1 (p=0.277) and Lin28a (p=0.051) were similarly expressed between the groups. Bcl2 was expressed in 38 SCLC patients (46.3%) and in 17 EPNEC patients (28.3%; p=0.030). Only in the EPNEC group, Bcl2 high expression was associated with worse survival (8.0 months vs 14.7 months; p = 0.025). RR to chemotherapy was not influenced by the expression of the ERCC1, Lin28a, Bcl-2, Ki-67 in either EPNEC or SCLC groups. CONCLUSION: Even though SCLC and EPNEC are treated similarly, in this cohort, the rate response differed significantly. When compared with SCLC, patients with EPNEC apparently had tumors less responsive to platin-based chemotherapy, but tended to live longer. In EPNEC treated with platin, high expression of Bcl2 was associated with poor prognosis. We could not identify additional predictive or prognostic biomarkers
Piton, Nicolas. "Optimisation de la prise en charge diagnostique, pronostique et théranostique des carcinomes broncho-pulmonaires humains : des techniques d’imagerie in vivo à la biologie moléculaire. Ligation -dependent RT-PCR : a new specific and low-cost technique to detect ALK, ROS and RET rearrangements in lung adenocarcinoma A new assay for detection of theranostic gene translocations and MET exon 14 skipping in thoracic oncology. One-year perspective routine LD-RT-PCR in 413 newly diagnosed lung tumors STK11 mutations are associated with lower PDL1 expression in lung adenocarcinoma BRAF V600E mutation is not always present as expected ! A case report of lung and thyroid carcinomas A novel method for in vivo imaging of solitary lung nodules using navigational bronchoscopy and confocal laser microendoscopy." Thesis, Normandie, 2019. http://www.theses.fr/2019NORMR119.
Повний текст джерелаLung cancer is a serious and frequent condition for which the management strategies have been dramatically modified in recent years, from a diagnostic, prognostic and “theranostic” perspective, most notably with the introduction of “targeted therapies”. The latter have demonstrated dramatic improvement in both quality of life and survival rates of eligible patients, yet consequently highlight new complications in diagnosis, treatment options or technical considerations which can be attributed to the growing number of molecular alterations to be detected from limited tissue samples frequently encountered in thoracic oncology. This work combines 5 different research papers from 2 different angles: prognostic and “theranostic” molecular markers of lung cancer, as well as in vivo diagnostic procedures of lung cancer. The first angle encompasses 4 articles. The first two evaluate a new molecular technique, LD-RT-PCR, to detect gene translocation in lung cancer. The third article explores the association between STK11 mutations in lung cancer and the expression of PDL1. Finally, the fourth article is a case report illustrating the importance of a morphological approach to lung cancer. The second angle compares in vivo imaging techniques by endoscopy using confocal laser microendoscopy alongside a conventional microscopic approach
Terlizzi, Michela. "Role of the inflammasome in lung cancer Inflammasome is involved in lung carcinogenesis." Doctoral thesis, Universita degli studi di Salerno, 2017. http://hdl.handle.net/10556/2410.
Повний текст джерелаLung cancer is recognized as one of the most devastating tumor worldwide due to the low rate survival over 5 years from the time of diagnosis. Inflammation has been widely recognized as the seventh hallmark of cancer as it facilitates the establishment/development and progression of lung cancer. In this context, recent evidence highlighted the role of the inflammasome during carcinogenesis. However, little is still known. The inflammasome is a multiprotein complex that leads to caspase-1 activation which role in lung cancer is still under investigated. In this context, the aim of my PhD project was to understand the role of the inflammasome in lung cancer in a mouse model of carcinogen-induced lung cancer and in human non-small cell lung cancer (NSCLC). We found that both caspase-1-dependent, the canonical pathway, and caspase-8/caspase-11-dependent, the non-canonical pathway, inflammasome were involved during lung cancer establishment and progression in both mice and humans. Our data showed that the pharmacological inhibition of both caspase-1 and caspase-8 significantly reduced lung tumor outgrowth associated to lower pro-inflammatory response and to a reduced lung recruitment of immunesuppressive cells and that caspase-8 was upstream caspase-1 activation during lung carcinogenesis. Furthermore, we showed that caspase-11 was the primary/main orchestrator of the inflammasome-dependent lung cancer progression and that the enzyme could be upstream of caspase-1 to induce the amplification of the occurring inflammatory process associated to lung cancer development. Finally, we identified a novel mechanism by which lung tumor-associated macrophages could favor lung tumorigenesis via the activation of caspase-11-dependent inflammasome and the consequent release of the pro-tumorigenic IL-1α. [edited by author]
XIV n.s.
Moraes, Adriel dos Santos 1976. "Administração de nanotubos de carbono "multiwalled" in vivo ativa citotoxicidade tumor-específica de linfócitos T CD8+." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/259942.
Повний текст джерелаDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação
Made available in DSpace on 2018-08-20T09:27:39Z (GMT). No. of bitstreams: 1 Moraes_AdrieldosSantos_M.pdf: 1300108 bytes, checksum: bcd1099ef486cc4a2842627fe2b4df57 (MD5) Previous issue date: 2012
Resumo: A administração "in vivo" de nanotubos de carbono "multi-walled" (MWCNT's), mesmo sem serem funcionalizados, estimula o aparecimento de uma reposta imune em camundongos normais. Nesse trabalho nós fornecemos evidências de que essas nanopartículas de carbono também estimulam a resposta imune em camundongos portadores de tumor. Os MWCNT's (100 ?g) diluídos em PBS contendo 0,1 % de Pluronic 127 foram inoculados sistemicamente em camundongos portando tumores cujos tamanhos atingiram 5 milímetros (mm) e a resposta imune foi avaliada nos linfonodos desses animais. Observamos que os tumores de animais que receberam as nanopartículas não cresceram como os tumores dos animais não tratados. A discreta inibição do crescimento do carcinoma pulmonar de Lewis (LLC) foi acompanhada pela ativação de linfócitos T CD8+ tanto em número quanto em função. A ativação da função citotóxica dos linfócitos T CD8+ pode ser explicada pelo aumento da expressão de citocinas pertencentes à família da IL-12, principalmente IL-27, que é descrita como a citocina envolvida na estimulação da citotoxicidade de linfócitos T CD8+. Nossos dados demonstraram que nanotubos de carbono "multi-walled", mesmo sem funcionalização estimula resposta imunológica antitumoral
Abstract: The "in vivo" administration of multi walled carbon nanotubes (MWCNT's) even without functionalization stimulates the immune response of naïve mice. Here we provide evidence that these carbon nanoparticles also stimulated the immune response of tumor-bearing mice. The MWCNT's (100 ?g) diluted in PBS with 0,1% of Pluronic 127 were inoculated systemically in mice with tumor that reached 5 mm and the immune response was evaluated in the lymph nodes. We observed that the tumors that received the nanoparticles did not grow as the untreated tumor. The discrete inhibition of the growth of the Lewis Lung Carcinoma (3LL) was accompanied by activation of CD8 T lymphocytes both in number and in function. The activation of the cytotoxic function of CD8 T lymphocytes may be explained by the increase of expression of cytokines belongs to the IL-12 family, mainly the IL-27, which is described as a cytokines involved in the stimulation of CD8 T lymphocytes cytotoxic function. Our data demonstrated that MWCNT even without functionalization stimulated the antitumor immune response
Mestrado
Eletrônica, Microeletrônica e Optoeletrônica
Mestre em Engenharia Elétrica
Yan, Dejun. "THE EFFECT OF CURCUMIN ON LEWIS LUNG CARCINOMA." Bowling Green State University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1308588440.
Повний текст джерелаRitchie, Andrew John. "Endocrinology, oncogene expression and outcome in carcinoma of the lung." Thesis, Queen's University Belfast, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357457.
Повний текст джерелаNahreini, Piruz. "Regulation of Lewis lung carcinoma cell growth by prostaglandins." Virtual Press, 1985. http://liblink.bsu.edu/uhtbin/catkey/424559.
Повний текст джерелаWright-Perkins, Shirley. "Characteristics and interrelationships of cell lines derived from an undifferentiated bronchial carcinoma." Thesis, University of Liverpool, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317361.
Повний текст джерелаMcLean, John S. "The modulation of the phenotype of human-non-small cell lung cancer." Thesis, University of Glasgow, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.236727.
Повний текст джерелаNordman, Ina IC Clinical School St Vincent's Hospital Faculty of Medicine UNSW. "Surrogate endpoints of survival in metastatic carcinoma." Publisher:University of New South Wales. Clinical School - St Vincent's Hospital, 2008. http://handle.unsw.edu.au/1959.4/42791.
Повний текст джерелаSirzén, Florin. "Molecular aspects of cellular radiosensitivity in small cell lung carcinoma /." Stockholm, 1998. http://diss.kib.ki.se/1998/19981204sirz/.
Повний текст джерелаWheeler, Elizabeth H. "Natural killer cell activity in mice bearing Lewis lung carcinoma." Virtual Press, 1985. http://liblink.bsu.edu/uhtbin/catkey/416656.
Повний текст джерелаCulak, Renata A. "Characterisation of selected sialoglycoproteins isolated from human lung carcinoma cells." Thesis, University of East London, 2001. http://roar.uel.ac.uk/3572/.
Повний текст джерелаHemström, Anna Therése Helén. "Apoptosis, cellular division or mitotic catastrophe? : effects of kinase inhibition and DNa damage in lung cancer cells /." Stockholm, 2006. http://diss.kib.ki.se/2007/978-91-7357-031-2/.
Повний текст джерелаEkedahl, Jessica. "Apoptotic signaling in lung carcinoma cells with focus on mechanisms of radioresistance /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-502-6/.
Повний текст джерела林華杰 and Wah-kit Lam. "A clinical and epidemiological study of carcinoma of lung in HongKong." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1985. http://hub.hku.hk/bib/B31981264.
Повний текст джерелаProchazka, Michaela. "The risk of second primary lung carcinoma in breast cancer patients /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-649-2/.
Повний текст джерелаChu, Ka-wan Kevin. "High-throughput molecular characterization of human non-small cell lung carcinoma /." View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38165107.
Повний текст джерелаChu, Ka-wan Kevin, and 朱嘉運. "High-throughput molecular characterization of human non-small cell lung carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B4501288X.
Повний текст джерелаLorch, Gwendolen. "Mechanisms of Receptor-Mediated Hypercalcemia in Human Lung Squamous Cell Carcinoma." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1242659291.
Повний текст джерелаLam, Wah-kit. "A clinical and epidemiological study of carcinoma of lung in HongKong." [Hong Kong : University of Hong Kong], 1985. http://sunzi.lib.hku.hk/hkuto/record.jsp?B12318061.
Повний текст джерелаChatterjee, Saradiya. "Role of TLR7 in non-small cell lung carcinona (NSCLC)." Paris 6, 2013. http://www.theses.fr/2013PA066063.
Повний текст джерелаLung cancer accounts for over 1 million deaths per year with a 5-year survival of 8-12%. Stimulation of TLRs by the natural ligands like the PAMPs and DAMPs results in a proinflammatory signaling cascade. We have shown that stimulation of lung cancer cell lines with TLR7 agonist lead to tumor cell survival and chemoresistance in vitro. We studied the effect of TLR7 agonists on A549 and LL/2 cells injected in NOD/SCID and C57BL/6 mice either treated or not with cisplatin. Loxoribine has a pro-tumoral effect on A549 cells and induces chemoresistance in NOD/SCID mice. Blockade of TLR7 with IRS661 reversed the pro-tumoral effect of TLR7 agonist on A549 cells. CL264 was also found to have a pro-tumoral effect on LL/2 cells and induced chemoresistance in NOD/SCID mice. On the other hand CL264 at lower concentration induces an anti-tumoral effect on LL/2 cells while at a higher concentration demonstrated a pro-tumoral effect in C57BL/6 mice. We also demonstrated an overall bad prognostic value for higher expression of TLR7 by tumoral cells among NSCLC patients treated and not treated with neoadjuvant chemotherapy. These results suggest a pro- tumoral role and induction of chemoresistance by TLR7 in NSCLC patients. Use of TLR7 agonist as therapeutic option is recommended based on the TLR7 expression level for individual NSCLC patients. TLR7 antagonist holds promise for treatment of NSCLC in future
Aguirre, Egaña Itziar de. "LKB1/ AMPK / TSC2 signaling pathway alterations in non-small-cell-lung-carcinoma." Doctoral thesis, Universitat Autònoma de Barcelona, 2014. http://hdl.handle.net/10803/284322.
Повний текст джерелаLKB1, also known as STK11b, is a serine/threonine kinase that functions as a suppressor of tumor growth. Germ line mutations in LKB1 are associated with the Peutz-Jeghers syndrome (PJS), an autosomal dominant disorder characterized by benign hemartomas of the gastrointestinal tract and mucocutaneous melanin deposits and an increased risk of certain cancers, including lung. The main PJS locus has been mapped to chromosome 19p13.3, and the gene responsible was identified as LKB1. Mutations in LKB1 gene are also associated with sporadic lung adenocarcinomas and occurs in approximately one-third of primary tumors and half of lung adenocarcinoma cells lines, implicating LKB1 in the pathogenesis of lung cancer. Recent evidence suggests that LKB1 signaling plays a role in protecting cells from apoptosis in response to energy or nutrient deprivation, which is achieved in part through the suppression of mTOR activity. Evidence from the literature supports a protein kinase cascade model in which LKB1 phosphorylates AMPK. AMPK is a heterotrimeric complex comprising a catalytic subunit (α) and two regulatory subunits (β and γ) that act as an intracellular energy sensor maintaining the energy balance within the cell. AMPK subsequently phosphorylates TSC2. Together the TSC1-TSC2 heterodimer acts to suppress the activity of mTOR, which is essential for the control of cell growth and proliferation. Thus, LKB1 functions as a negative regulator of mTOR. Additionally, LKB1 has been shown to regulate 11 of the 12 AMPK family members in vitro, suggesting that one of the tumour suppressor functions of LKB1 may be regulation of AMPK signaling. Therefore, LKB1 could be a potential target for treatment of both cancer and metabolic disorders. In this work we sought to study the signal transduction LKB1/AMPK/TSC2 pathway alterations that contribute to the pathogenesis NSCLC. Our major objectives were: ▪To determine the frequency of genetic and epigenetic alterations in the signal traduction LKB1/AMPK/TSC2 pathway in NSCLC in a panel of 23 cell lines (4 normal bronchial epithelial cell lines immortalized with SV40 and 19 NSCLC cell lines). ▪ To study some components of AMPK-related kinase family that could be activated downstream of LKB1, in particular we analyzed the methylation status of: BRSK1, BRSK2, MARK1, MARK4 in our panel of 23 cell lines. ▪ To examine LKB1/BRSK2 signaling.▪ To make a clinical validation of BRSK2 methylation status, in 58 FFPE of patients with NSCLC. ▪ To determinate the impact of LKB1 depletion on NSCLC cell lines. The major conclusions of this work were: ▪ LKB1 mutations are not confined to adenocarcinomas, they also occur in other NSCLC subtype such as large cell carcinomas. But we found no evidence of LKB1 methylation in any NSCLC cell lines used in this study. ▪ There are not sequence alterations or/and promoter methylation of AMPK and TSC components studied in our 23 panel cell lines. ▪ Of the four AMPK related kinases -BRSK1, BRSK2, MARK1 and MARK4- studied, BRSK2 represents the highest percentage of methylation; ~26 % of NSCLC cell lines and 25.8% in the 58 NSCLC samples. ▪ BRSK2 methylation is significantly correlated with four clinicopatological parameters: tumor stage (P=0,025), histology (P=0,001), tumor size (P=0,073) and nodules affected (P=0,04), suggesting that methylation of BRSK2 could provide a novel biomarker for disease progression in lung cancer. ▪ The disruption of LKB1/BRSK2 signaling could be important in the carcinogenesis of lung, as a molecular mechanism for the development of lung cancer.
Fenwick, Jill. "A quantitative multiparametric cytochemical analysis of small cell carcinoma of the lung." Thesis, Liverpool John Moores University, 1997. http://researchonline.ljmu.ac.uk/4901/.
Повний текст джерелаCasadevall, Aguilar David. "Heterogeneity of biomarker expression in non-small cell lung cancer." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/457975.
Повний текст джерелаThe success of precision medicine in oncology is dependent to a large extent on an adequate selection of patients who will receive targeted therapies aimed at specific molecular traits of their tumor. In order to be able conduct such patient selection, predictive biomarkers that can inform therapeutic decisions are essential. MET and PD-L1 are two relevant membrane receptors for non-small cell lung cancer (NSCLC) biology. MET is an oncogene the activation of which is involved in multiple pro-tumorigenic processes such as cell proliferation, motility and invasion. PD-L1 is a key molecule that acts during the immune response, and its overexpression in tumors is thought to mediate the ability of tumor cells to avoid immune cell recognition and destruction. Currently, there are specific therapies directed against these molecules. The most commonly used strategy to select the patients that will benefit from such drugs is the analysis of the expression of both molecules in tumor tissue. However, the value of MET and PD-L1 as predictive biomarkers and the method by which it should be determined is a subject of debate. Recent studies have detected a high degree of genomic heterogeneity in NSCLC tumor samples. This heterogeneity could significantly affect biomarker-based patient classification especially in the case of NSCLC, since biomarker studies are usually performed in small biopsies or cytology samples obtained through minimally invasive techniques. The main objective of the work presented in this thesis is to study the heterogeneity of the expression of MET and PD-L1 in NSCLC samples. For this purpose, we have analyzed tumor samples from NSCLC patients that had undergone surgical treatment at Hospital del Mar. Of each tumor, we have selected multiple geographically separate areas, which we analyzed independently. In the study evaluating MET, we selected four tumor areas per patient, while in the study evaluating PD-L1 we selected two areas. In each tumor area, we measured the expression MET and PD-L1 using immunohistochemical and fluorescence in situ hybridization methods (FISH). Finally, we compared the expression of MET and PD-L1 in different tumor areas. Regarding MET, we have found discordances between different tumor areas in 20-40% of cases using immunohistochemistry and in 25-50% of cases using FISH. Regarding PD-L1, this discrepancy was greater if we evaluated PD-L1 expression in tumor infiltrating lymphocytes (17-27%) than if we did so only in tumor cells (10-19%). Moreover, 36% of the cases with amplification of the gene coding for PD-L1 determined by FISH presented gene amplification only in one of the two areas analyzed. Overall, our results suggest that the expression of both biomarkers is heterogeneous, whether measured by immunohistochemistry or by FISH. This heterogeneity can have a potential impact on the classification of tumors based on the expression of biomarkers and, therefore, could represent a hurdle for the development of targeted therapies for NSCLC patients.
Fernández, Araujo Esther. "Carcinoma broncogénico. supervivencia quirúrgica de pIIIpN2." Doctoral thesis, Universitat Autònoma de Barcelona, 2018. http://hdl.handle.net/10803/664284.
Повний текст джерелаManagement of Stage IIIA-N2 non-small-cell lung cancer (NSCLS) that represents locally advanced disease with the involvement of ipsilateral mediastinal lymph nodes remains highly controversial and is hotly debated during every major conference of thoracic oncology and surgery. The main reason is that Stage IIIA-N2 NSCLS is not a homogeneous disease entity and comprises quite distinct subgroups. The most studies shows a 5-year survival between 6-35% after surgery alone. Although unexpected N2 seems to have a better overall survival. The aim of this study is to analyze the survival of patients NSCLS without clinical suspicion of mediastinal lymph node involvement who underwent complete resection and whose lung cancer were finally proven to be pathologic N2 (pN2). We analyze the survival in this subjects: one pN2 station vs multiple pN2 station, survival in patients with pN1 + pN2, survival in squamous cell and adenocarcinoma in patients pN2, T factor and pN2 and upper lobes lung cancer and upper mediastinal lymph node pN2. This is a retrospective study that includes two series. Serie 1 from 1995 to 2001 and series 2 from 2008 to 2011. A total of 121 patients unexpected pN2 in series 1 and 31 patients unexpected pN2 in series 2 were analyzed. 5-year survival rates were 18% and 40% respectively and that’s the first bigger difference between two series. In both series we met a better survival in only one pN2 station versus multiples pN2 stations and a also a better survival in right upper lobe lung cancer and 4R lymph node involvement and a trend to a better survival in upper left lobe lung cancer and 5-6 involvement. We cannot demonstrate a better survival in patients with “skip metastasis”. We also cannot identify a correlation between histology and T status with pN2. In conclusion the rate of unsuspected pN2 in recent patients is low thanks to the introduction of new technology for staging lung cancer as PET-TAC and EBUS. Therefore, resection of properly staged unexpected pN2 NSCLC is reasonable and should not be avoided especially if a lobectomy is feasible.
Näpänkangas, U. (Ulla). "Apoptosis in non-small cell carcinoma and preinvasive bronchial lesions of the lung." Doctoral thesis, Oulun yliopisto, 1999. http://urn.fi/urn:isbn:9514253302.
Повний текст джерелаKazawa, Nobutaka. "Small cell lung carcinoma : eight types of extension and spread on computed tomography." Kyoto University, 2007. http://hdl.handle.net/2433/135905.
Повний текст джерелаEerola, A. K. (Anna-Kaisa). "Apoptosis and apoptosis regulating proteins and factors in small and large cell lung carcinoma." Doctoral thesis, University of Oulu, 1999. http://urn.fi/urn:isbn:9514254066.
Повний текст джерелаFujimoto, Masakazu. "Stromal plasma cells expressing immunoglobulin G4 subclass in non-small cell lung cancer." Kyoto University, 2015. http://hdl.handle.net/2433/199170.
Повний текст джерелаCosaceanu, Daria. "The use of IGF-IR inhibitors in cancer therapy - a potential approach for sensitizing tumor cells to ionizing radiation /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-911-4/.
Повний текст джерелаVincent, Emma Elizabeth. "The role of AKT signalling in insulin resistance and non-small-cell lung carcinoma." Thesis, University of Bristol, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.520254.
Повний текст джерелаSkrzypek, Klaudia. "Role of microRNAs in non-small cell lung carcinoma : effect of heme oxygenase-1." Thesis, Orléans, 2013. http://www.theses.fr/2013ORLE2001.
Повний текст джерелаHeme oxygenase-1 (HO-1), an antioxidant enzyme can prevent tumor initiation while it has been demonstrated to promote various tumors progression and angiogenesis. Here it was investigated whether HO-1 can modulate microRNAs and regulate human non-small cell lung cancer (NSCLC) development. Stable HO-1 overexpression in NSCLC NCI-H292 cells enhanced global production of miRNAs and significantly diminished expression of oncomirs and angiomirs, whereas upregulated tumor suppressive miRNAs. The most potently downregulated was miR-378. HO-1 overexpressing cells displayed also upregulated p53, downregulated Ang-1 and MUC5AC, reduced proliferation, migration and diminished angiogenic potential. CO was a mediator of HO-1 effects on tumor cells proliferation, migration and miR-378 expression. In contrast, stable miR-378 overexpression decreased HO-1 and p53 while enhanced expression of MUC5AC, VEGF, IL-8 and Ang-1 and consequently increased proliferation, migration and stimulation of endothelial cells. Adenoviral delivery of HO-1 to miR-378 overexpressing cells reversed miR-378 effect on proliferation and migration of cancer cells. In vivo, HO-1 overexpressing tumors were smaller, less vascularized and oxygenated and less metastatic, whereas miR-378 overexpression exerted the opposite effects. Accordingly, in patients with NSCLC, HO-1 expression was lower in metastases to lymph nodes than in primary tumors while miR-378 did not differ significantly. To conclude, in vitro and in vivo data indicate that interplay between HO-1 and miR-378 significantly modulates NSCLC progression and angiogenesis
Hakami, Fahad Mohammad I. "The role of the homeobox gene HOXD10 in lung and head & neck carcinoma." Thesis, University of Sheffield, 2013. http://etheses.whiterose.ac.uk/5957/.
Повний текст джерелаTertil, Magdalena. "Role of thymidine phosphorylase and Nrf2 transcription factor in non-small cell lung carcinoma growth and angiogenesis." Thesis, Orléans, 2013. http://www.theses.fr/2013ORLE2043.
Повний текст джерелаNrf2, heme oxygenase-1 (HO-1) and thymidine phosphorylase (TP) are considered as potential targets for combinatorial anti-cancer therapies. The aim of the study was to investigate the interplay of these proteins in regulation of growth and angiogenesis in non-small cell lung carcinoma (NSCLC) cells NCI-H292. Stable overexpression of Nrf2 (NCI-Nrf2 cell line) resulted in decreased cell proliferation and migration in vitro, upregulation of tumor suppressor microRNAs and downregulation of oncogenic miR-378 and many MMPs. Silencing of HO-1 in NCI-Nrf2 cells partially reversed the effect on MMP-1, MMP-3 and miR-378. NCI-Nrf2 cells exhibited increased expression of proangiogenic factors IL-8, angiopoietin-1 and TP, which was also upregulated in cell overexpressing HO-1. In both models, the effect was TP reversible by siRNA targeted at HO-1 and possibly mediated by modulation of oxidative status of the cell. Moreover, it was observed that overexpression of TP in vitro attenuated proliferation and migration of NSCLC cells, but increased their angiogenic potential. In vivo, NCI-TP tumors tended to grow faster, were better oxygenated and exhibited increased expression of inflammatory cytokines IL-1β and IL-6. Correlation of TP with IL-1β and IL-6 was also confirmed in clinical samples from NSCLC patients. Overall, our results enforce the notion of targeting TP for treatment of NSCLC
Ko, Adrien. "Impact de l’autophagie sur la radiosensibilité tumorale." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T074.
Повний текст джерелаMost of the available data on autophagy and tumor response to IR comes from indirect conclusions after concomitant drug-IR exposure. Some authors suggest that concurrent induction of apoptosis and autophagy enhances radiation therapy. Oppositely, others indicate that the induction of autophagy contributes to the radioresistance of tumor cells and suggest that autophagy inhibitors may be employed to increase the sensitivity radioresistant tumors cells to ionizing radiation. Autophagy literally ‘self-eating’ is a cellular process activated in response to various conditions of cellular stress, whereby cells can liberate energy resources via the degradation of proteins and organelles. In this project we aimed to determine the potential role of autophagy in IR –induced cell death. We found that autophagy is required for the release of ATP in response to radiotherapy, as we observed that the knockdown of essential autophagy-related genes abolished its secretion. Furthermore, autophagy deficient tumors growing on immunocompetent mice did not respond to radiotherapy and continued proliferating in contrast to autophagy proficient tumors. We showed that autophagy deficient cells were neither able to recruit DCs into the tumor bed. Conversely, the inhibition of extracellular ATP degrading enzymes increased extracellular ATP concentrations in autophagy deficient tumors, which reestablished the recruitment of immune cells into the tumor bed, and restored radiotherapeutic responses in autophagy-deficient cancers.Altogether, this study showed the importance of autophagy in tumor-specific immune response after radiotherapy. Thus giving new insights into the concept of IR-induced cell death. However, there is still much that is unknown about molecular mechanisms that undergo IR-induced cell death. Understand these molecular mechanisms will help to develop new targeted therapies that will improve the effectiveness of radiotherapy
Cui, Tao. "Novel Circulating and Tissue Biomarkers for Small Intestine Neuroendocrine Tumors and Lung Carcinoids." Doctoral thesis, Uppsala universitet, Onkologisk endokrinologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-205570.
Повний текст джерела小肠神经内分泌肿瘤(SI-NET)和肺类癌(LC)是起源于不同神经内分泌细胞的生长缓慢的肿瘤。肿瘤往往于诊断前已经转移。这导致目前缺乏有效的治疗方法,同时也使得对于新的生物标记物的研发变得有意义。因此,我们在本论文中分别研究了Ma2自身抗体(抗Ma2),以及潜在的新型生物标记物嗅觉受体51E1(OR51E1)。我们还探讨了患者血清中的其他候选蛋白标记物。 首先,我们建立了一个灵敏特异而可靠的抗Ma2间接酶联免疫吸附试验,用以区分SI-NET患者组和健康对照组。在表达低滴度抗Ma2的患者中,我们检测到了较长的病情无恶化存活率以及肿瘤无复发存活率。此外,高滴度抗Ma2比嗜铬粒蛋白A更为灵敏地检测到了SI-NET患者根治手术后复发的风险。 接下来,我们研究了SI-NET和LC患者肿瘤中的OR51E1受体蛋白的表达。我们用实时定量PCR技术检测到了OR51E1信使核糖核酸在显微切除的SI-NET肿瘤细胞中,以及在LC细胞系和冷冻LC标本中的高度表达。免疫组化结果显示出OR51E1蛋白在SI-NET肿瘤组织中的高度表达。OR51E1与囊泡单胺转运蛋白1在大多数正常和肿瘤的肠嗜铬细胞中可共表达。 另外,我们针对LC患者的研究显示,OR51E1受体蛋白以及促生长素抑制素受体(SSTR)2,SSTR3和SSTR5分别在85%,71%,25%和39%的典型性肺类癌(TC),以及86%,79%,43%和36的非典型性肺类癌(AC)中表达。基于我们我提出的免疫组化结果得分系统,在无SSTR表达的LC中,OR51E1蛋白在17个TC中的10个以及2个AC中的1个中呈细胞膜表达。而且,在6个OctreoScan显象呈阴性的LC中,有5个OR51E1免疫组化得分很高。 此外,在本论文最后的一项研究中,我们采用了一种新型的悬浮磁珠阵列技术,通过使用来自于人类蛋白质图谱项目的针对124种独特蛋白质的抗体,对SI-NET患者和健康对照组的用生物素标记过的血清样本进行了分析。结果显示,通过利用9种蛋白,即IGFBP2,IGF1,SHKBP1,ETS1,STX2,IL1α,MAML3,EGR3和XIAP,我们可以显著的对肿瘤进行分类。 综上所述,我们提出Ma2自身抗体可作为一个体液中灵敏的生物标记物用以暗示SI-NET肿瘤的复发; OR51E1受体蛋白可作为一个在SI-NET治疗中所能用及的候选生物靶分子,并在LC中作为一种新型的潜在生物标记物。此外,我们在SI-NET患者血清中检测到了9种新的候选标记物蛋白。
Oliveira, Ana Maia Cerqueira Sarmento. "Molecular Subtyping of Lung Carcinomas for Targeted Therapy." Master's thesis, 2012. https://repositorio-aberto.up.pt/handle/10216/65207.
Повний текст джерелаOliveira, Ana Maia Cerqueira Sarmento. "Molecular Subtyping of Lung Carcinomas for Targeted Therapy." Dissertação, 2012. https://repositorio-aberto.up.pt/handle/10216/65207.
Повний текст джерелаCheng, Ai-ling, and 程愛淩. "Frequent Inactivation of LKB1 in Human Non-Small Cell Lung Carcinomas." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/89565221110383155096.
Повний текст джерела國立中山大學
生物醫學科學研究所
93
Lung cancer is the second leading cause of cancer-related death in Taiwan in 2003. However, lung cancer has become the first in 2004. Discovering the new molecular targets may provide new methods for the treatments of this devastating disease. LKB1, a serine/threonine kinase, is a new tumor suppressor gene with spontaneous mutations and/or deletions found in human cancers. Reports have recently demonstrated that LKB1 inactivating mutations in lung adenocarcinomas of sporadic origin, including primary tumors and lung cancer cell lines. In this study, we investigated LKB1 gene inactivation frequencies in 110 Taiwan patients with non-small cell lung carcinomas (NSCLC) and 7 lung cancer cell lines. LKB1 inactivation was screened by polymerase chain reaction (PCR), sequencing, co-amplification and loss of heterozygosity (LOH) analysis. In addition, LKB1 expressions were determined in clinical samples by immunohistochemistry (IHC) and in cell lines by reverse-transcriptase PCR and western blot analysis. The results showed five out of 110 (4.5%) patients with LKB1 gene exon 8 deletions. Two out these 5 patients were also found with exon 7 deletions. An identical mutation at codon 354 (Phe to Leu) were found in 4 out of 65 (6.2%) patients. The nature of this mutation was found to be a new LKB1 polymorphism by single strand conformation polymorphism (SSCP) assay and sequencing analysis after compared to normal controls. Various point mutations were also found in 3 out of 7 cell lines. In addition, 11 out of 81 (13.6%) patients were found with LOH. Finally, reduced expressions of LKB1 were observed in lung cancer clinical samples. These data suggest that LKB1 may be a tumor suppressor gene that involved in the carcinogenesis of NSCLC.