Open AccessJournal Article
Establishment and Identification of Small Cell Lung Cancer Cell Lines Having Classic and Variant Features
Desmond N. Carney,Adi F. Gazdar,Gerold Bepler,John G. Guccion,Paul J. Marangos,Terry W. Moody,Mark H. Zweig,John D. Minna +7 more
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TLDR
Using a chemically defined medium containing hydrocortisone, insulin, transferrin, 17 beta-estradiol and selenium, with or without serum supplementation, continuous cell lines can be established from 72% of all fresh biopsy specimens of small cell lung cancer containing tumor cells.Abstract:
Using a chemically defined medium containing hydrocortisone, insulin, transferrin, 17 beta-estradiol and selenium, with or without serum supplementation (2.5% v/v), continuous cell lines can be established from 72% of all fresh biopsy specimens of small cell lung cancer (SCLC) containing tumor cells. No differences were observed in the rate of establishing cell lines from newly diagnosed untreated patients, or from patients who have relapsed from prior therapy, or from a variety of different organ sites. Biochemical characterization of 50 SCLC cell lines for the expression of L-dopa decarboxylase; bombesin-like immunoreactivity; neuron-specific enolase, and the brain isozyme of creatine kinase, revealed that SCLC cell lines can be subdivided into two distinct classes: classic SCLC cell lines (35 lines), which express elevated levels of all four biomarkers; and variant SCLC cell lines (15 lines) which have undetectable levels of L-dopa-decarboxylase and bombesin-like immunoreactivity, but continue to express neuron-specific enolase and the brain isozyme of creatine kinase. The presence of the latter two markers distinguishes variant lines fron non-SCLC cell lines. In addition, four distinct classes were identified morphologically. The biomedical differences among established SCLC cell lines may account for the differences in response rates to cytotoxic therapy observed in newly diagnosed SCLC patients. A prospective study of biomarker characterization of SCLC tumors will determine if clinical differences exist between classic and variant SCLC tumors.read more
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Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing.
TL;DR: The clonogenic assay was more sensitive when continuous drug exposures were utilized, although this was primarily related to the increased drug exposure time, and therefore it offers a valid, simple method of assessing chemosensitivity in established cell lines.
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Feasibility of Drug Screening with Panels of Human Tumor Cell Lines Using a Microculture Tetrazolium Assay
Michael C. Alley,Dominic A. Scudiero,Anne Monks,Miriam L. Hursey,Maciej Czerwinski,Donald L. Fine,B. J. Abbott,Joseph G. Mayo,Robert H. Shoemaker,Michael R. Boyd +9 more
TL;DR: Since the microculture tetrazolium assay provides sensitive and reproducible indices of growth as well as drug sensitivity in individual cell lines over the course of multiple passages and several months' cultivation, it appears suitable for initial-stage in vitro drug screening.
Journal ArticleDOI
Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer.
Frank Cuttitta,Desmond N. Carney,James L. Mulshine,Terry W. Moody,Joseph Fedorko,Adam Fischler,John D. Minna +6 more
TL;DR: It is demonstrated that a monoclonal antibody to bombesin binds to the C-terminal region of BLPs, blocks the binding of the hormone to cellular receptors and inhibits the clonal growth of SCLC in vitro and the growth ofSCLC xenografts in vivo.
Journal ArticleDOI
p53: a frequent target for genetic abnormalities in lung cancer
Takashi Takahashi,Marion M. Nau,Itsuo Chiba,Michael J. Birrer,Richard K. Rosenberg,Michelle Vinocour,Mark L. Levitt,Harvey I. Pass,Adi F. Gazdar,John D. Minna +9 more
TL;DR: These findings, coupled with the previous demonstration of 17p allele loss in lung cancer, strongly implicate p53 as an anti-oncogene whose disruption is involved in the pathogenesis of human lung cancer.
Journal ArticleDOI
A small-cell lung cancer genome with complex signatures of tobacco exposure
Erin Pleasance,Philip J. Stephens,Sarah O’Meara,Sarah O’Meara,David J. McBride,Alison M. Meynert,David T. Jones,Meng-Lay Lin,David Beare,King Wai Lau,Christopher Greenman,Ignacio Varela,Serena Nik-Zainal,Helen Davies,Gonzalo R. Ordóñez,Laura Mudie,Calli Latimer,Sarah Edkins,Lucy Stebbings,Lina Chen,Mingming Jia,Catherine Leroy,John Marshall,Andrew Menzies,Adam Butler,Jon W. Teague,Jonathon Mangion,Yongming A. Sun,Stephen F. McLaughlin,Heather E. Peckham,Eric F. Tsung,Gina Costa,Clarence Lee,John D. Minna,Adi F. Gazdar,Ewan Birney,Michael D. Rhodes,Kevin McKernan,Michael R. Stratton,Michael R. Stratton,P. Andrew Futreal,Peter J. Campbell,Peter J. Campbell +42 more
TL;DR: Using massively parallel sequencing technology, a small-cell lung cancer cell line, NCI-H209, is sequenced to explore the mutational burden associated with tobacco smoking and identifies a tandem duplication that duplicates exons 3–8 of CHD7 in frame, and another two lines carrying PVT1–CHD7 fusion genes, indicating that ChD7 may be recurrently rearranged in this disease.
References
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Journal ArticleDOI
Amplification and expression of the c- myc oncogene in human lung cancer cell lines
TL;DR: In this article, the amplification and expression of the c-myc oncogene in a system other than B-cell lymphomas, namely human lung cancer, was reported.
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High levels of intracellular bombesin characterize human small-cell lung carcinoma.
TL;DR: "Small cells" or "oat cells" characterize a virulent form of lung cancer and share many biochemical properties with peptide-secreting neurones, suggesting that bombesinergic precursor cells in lung may give rise to this disease.
Journal Article
Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological, and growth properties.
TL;DR: Analysis of establishment and biochemical characterization of 50 small cell lung carcinoma (SCLC) cell lines indicates that 35 (70%) of the lines retained typical morphology, growth characteristics, and biochemical profile, and most SCLC-MV lines reflect changes that had occurred in the tumors from which they were derived.
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Specific chromosome defect associated with human small-cell lung cancer; deletion 3p(14-23)
Jacqueline Whang-Peng,C. S. Kao-Shan,E-Chiang Lee,Paul A. Bunn,Desmond N. Carney,Adi F. Gazdar,John D. Minna +6 more
TL;DR: A specific, acquired chromosomal abnormality (deletion 3p) has been found in at least one chromosome 3 in 100 percent of the metaphases in 12 of 12 cell lines cultured from human small-cell lung cancer tissue and in 2-day tumor culture specimens from three patients.
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Serum neuron-specific enolase: a marker for disease extent and response to therapy of small-cell lung cancer.
TL;DR: Serum neuron-specific enolase levels in 94 newly diagnosed untreated patients with small-cell lung cancer were compared with those in 30 adult controls to indicate that serum NSE may be a useful marker for staging and for monitoring response to therapy in patients with SCLC.