ライフサイエンスコーパス: SCLC

1 SCLC cell lines had a greater number of hypermethylated

2 SCLC cells secrete bombesin (BBS)-like neuropeptides tha

3 SCLC cells survived well and showed net proliferation an

4 SCLC is notable for dense clustering of high-level methy

5 SCLC is thought to derive from pulmonary neuroendocrine

6 so obtained data for 4 primary tumors and 23 SCLC cell lines.

7 Of 1,574 patients who had pT1-2N0M0 SCLC during the study period, 954 patients (61%) underwe

8 Patients with pT1-2N0M0 SCLC treated with surgical resection alone have worse ou

9 urvival of patients with pathologic T1-2N0M0 SCLC who underwent complete resection in the National Ca

10 ve to no adjuvant therapy for stage T1-2N0M0 SCLC.

11 Furthermore, in a SCLC patient-derived xenograft model that was resistant

12 Pharmacologic inhibition of EZH2 in a SCLC PDX markedly inhibited tumor growth.

13 In MYC-amplified SCLC cells Aurora kinase inhibition associates with G2/M

14 RNAs blocked proliferation of SOX2-amplified SCLC lines.

15 the immune cell contexture of lung ADCA and SCLC and suggest that molecular and histological traits

16 higher expression in atypical carcinoid and SCLC, and could be a new therapeutic target for SCLC.

17 SCLC has remained stagnant for decades, and SCLC is expected to persist as a threat to human health.

18 ently high to image established melanoma and SCLC xenografts using PSMA-based nuclear and optical ima

19 nonprostatic cancers including melanoma and SCLC.

20 Although NSCLC and SCLC are commonly thought to be different diseases owing

21 have described the coexistence of NSCLC and SCLC, further challenging the commonly accepted view of

22 In both NSCLC and SCLC, the use of modified radiotherapy increased the ris

23 ation changes that occur in primary SCLC and SCLC cell lines.

24 subset of NSCLCs with mutated EGFR return as SCLC when resistance to EGFR tyrosine kinase inhibitors

25 survival of a majority of lung cancers (both SCLC and NSCLC) with neuroendocrine features.

26 Small cell lung cancer (SCLC) accounts for about 15% of all lung cancers.

27 Treatments for small-cell lung cancer (SCLC) after failure of platinum-based chemotherapy are l

28 target expressed in small cell lung cancer (SCLC) and high-grade neuroendocrine carcinomas.

29 cancer, we show that small cell lung cancer (SCLC) and lung adenocarcinoma (ADCA) exhibit unique immu

30 g cancers, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), represent

31 een proposed in both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) to try to i

32 as single agents in small-cell lung cancer (SCLC) and other solid tumor malignancies, and rational c

33 s of origin of human small-cell lung cancer (SCLC) and recent mouse models support this hypothesis.

34 omplete resection of small-cell lung cancer (SCLC) are limited, and in particular, there have been no

35 Using small cell lung cancer (SCLC) as a model, we demonstrated the presence of differ

36 Small cell lung cancer (SCLC) at advanced stage is considered an incurable disea

37 d in the majority of small cell lung cancer (SCLC) cases and is associated with resistance to chemoth

38 bility of binding to small-cell lung cancer (SCLC) cell line H69 was studied in vitro.

39 romising activity in small-cell lung cancer (SCLC) in phase II trials.

40 Small cell lung cancer (SCLC) is a common, aggressive malignancy with universall

41 Small cell lung cancer (SCLC) is a devastating disease due to its propensity for

42 Small cell lung cancer (SCLC) is a devastating neuroendocrine carcinoma.

43 Small cell lung cancer (SCLC) is a devastating tumor type with great therapeutic

44 Small cell lung cancer (SCLC) is a difficult to treat subtype of lung cancer.

45 Small cell lung cancer (SCLC) is a disease characterized by aggressive clinical

46 Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor surviv

47 Small-cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with

48 r previously treated small-cell lung cancer (SCLC) is a major unmet need.

49 Small cell lung cancer (SCLC) is an aggressive cancer often diagnosed after it h

50 Small cell lung cancer (SCLC) is an aggressive disease with high mortality, and

51 Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early

52 Small-cell lung cancer (SCLC) is an exceptionally aggressive disease with poor p

53 Small cell lung cancer (SCLC) is characterized by prevalent circulating tumour c

54 mation from NSCLC to small-cell lung cancer (SCLC) is observed in a subset of the resistant cancers,

55 ated in Lu-iPSCs and small cell lung cancer (SCLC) lines and clinical specimens.

56 Fam38A expression in small cell lung cancer (SCLC) lines where a form of reduced integrin-dependent m

57 determination of the small cell lung cancer (SCLC) markers progastrin releasing peptide (ProGRP) and

58 afts of melanoma and small cell lung cancer (SCLC) origin.

59 to initial therapy, small-cell lung cancer (SCLC) relapse occurs within a year and exhibits resistan

60 Purpose Treating small-cell lung cancer (SCLC) remains a therapeutic challenge.

61 st-line treatment of small-cell lung cancer (SCLC) remains contentious, a meta-analysis of individual

62 mouse model of human small cell lung cancer (SCLC) to investigate the mechanisms that drive the metas

63 ted in patients with small-cell lung cancer (SCLC) undergoing standard treatment.

64 ingly, we found that small cell lung cancer (SCLC), a subtype of lung cancer with neuroendocrine char

65 Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor with early dis

66 atypical carcinoid, small cell lung cancer (SCLC), and large cell NE cancer.

67 Small cell lung cancer (SCLC), as a proportion, makes up only 15-17% of lung can

68 ss this question for small cell lung cancer (SCLC), finding that changes in genomic accessibility med

69 rgeted therapies for small-cell lung cancer (SCLC), the most aggressive form of lung cancer, remain u

70 s of lung cancer are small-cell lung cancer (SCLC), which is the cause of 15% of cases, and non-small

71 n most patients with small-cell lung cancer (SCLC)-a metastatic, aggressive disease-the condition is

72 ent of patients with small-cell lung cancer (SCLC).

73 r for acquisition of small cell lung cancer (SCLC).

74 t of extensive-stage small-cell lung cancer (SCLC).

75 oncogenic events in small cell lung cancer (SCLC).

76 tensive-disease (ED) small-cell lung cancer (SCLC).

77 extensive stage (ES) small-cell lung cancer (SCLC).

78 In small-cell lung cancer (SCLC; two trials, 685 patients), similar results were fo

79 y classified 98% of small cell lung cancers (SCLC) and non-SCLC patients [receiver operator character

80 the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers.

81 Small cell lung carcinoma (SCLC) is a highly lethal, smoking-associated cancer with

82 Small cell lung carcinoma (SCLC) is extremely aggressive and frequently metastasize

83 es indicated that small cell lung carcinoma (SCLC) is sensitive to LSD1 inhibition.

84 Small cell lung carcinoma (SCLC) often features the upregulation of the Sonic hedge

85 In a human small-cell lung carcinoma (SCLC) primary xenograft model, ME and CME compounds were

86 Cancer (majority small-cell lung carcinoma [SCLC]) was detected in 66 of 84 evaluated patients (79%)

87 In rare cases, SCLC tumours exhibited kinase gene mutations, providing

88 We discovered in CD133(+) SCLC cells, an increased expression of the mitogenic neu

89 cell genomic analysis reveals characteristic SCLC genomic changes in both VE-cadherin-positive and -n

90 ith either chemosensitive or chemorefractory SCLC are tumorigenic in immune-compromised mice, and the

91 regulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared with

92 and phenotypic characteristics of classical SCLC.

93 vation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumour

94 and biology underlying tumours with combined SCLC and NSCLC histology and cancers that transform from

95 Patients and Methods Patients with confirmed SCLC (limited or extensive disease) and performance stat

96 In concordance, cultured SCLC but not non-small cell lung carcinoma cells showed

97 the need to better understand this disease, SCLC remains poorly characterized at the molecular and g

98 l targeted treatment approach for MYC-driven SCLC.

99 ation of widespread chromatin changes during SCLC progression reveals an unexpected global reprogramm

100 etoposide in the first-line treatment of ED-SCLC had an acceptable toxicity profile and led to a sta

101 and Methods Treatment-naive patients with ED-SCLC were randomly assigned to receive either cisplatin

102 amide to CE failed to improve survival in ES SCLC.

103 Previously untreated patients with ES SCLC were randomly assigned in a 1:1 fashion to receive

104 In a group of 270 ES-SCLC cases retrospective study, 78 patients (28.9%) had

105 c extensive stage small-cell lung cancer (ES-SCLC) to the overall survival (OS).

106 h extensive stage small-cell lung cancer (ES-SCLC) who undergo chemotherapy, and prophylactic cranial

107 h extensive-stage small-cell lung cancer (ES-SCLC).

108 h WHO performance score 0-2 and confirmed ES-SCLC who responded to chemotherapy.

109 le addition of chemotherapy when treating ES-SCLC patients with oligometastases and polymetastases.

110 hould be considered for all patients with ES-SCLC who respond to chemotherapy.

111 immunotherapies as a potential approach for SCLC treatment.

112 noPET, can serve as an imaging biomarker for SCLC.

113 ith etoposide, a gold-standard cytotoxic for SCLC therapy.

114 erapy are independent prognostic factors for SCLC.

115 a have direct translational implications for SCLC clinical trials.

116 litate delivery of personalized medicine for SCLC.

117 ar but nonsignificant trend was observed for SCLC.

118 e that HIFs are not exclusively required for SCLC cell survival at modest or severe hypoxia and that

119 rovided effective therapeutic strategies for SCLC.

120 ion therapy may be an effective strategy for SCLC treatment, which warrants clinical testing.

121 s a potential immunotherapeutic strategy for SCLC.

122 The median survival for SCLC remained 7 months, and the 12-month relative surviv

123 hlight ASXL3 as a novel candidate target for SCLC therapy.

124 C, and could be a new therapeutic target for SCLC.

125 a CDK7 inhibitor, as a potential therapy for SCLC.

126 ersus topotecan as second-line treatment for SCLC.

127 The development of treatments for SCLC has remained stagnant for decades, and SCLC is expe

128 h has completed a phase I clinical trial for SCLC.

129 disorders and has high predictive value for SCLC.

130 VE-cadherin is required for VM in NCI-H446 SCLC xenografts, where VM decreases tumour latency and,

131 mics underlie the emergence of heterogeneous SCLC phenotypes.

132 expression was increased in mouse and human SCLC after chemotherapy, an observation confirmed in cli

133 LC tumorigenesis with implications for human SCLC therapeutics and the nature of cancer-genome evolut

134 ecule (NCAM), promoted phagocytosis in human SCLC cell lines that was enhanced when combined with CD4

135 YCL (L-Myc) is frequently amplified in human SCLC, but its roles in SCLC progression are poorly under

136 is highly expressed on the surface of human SCLC cells; therefore, we investigated CD47-blocking imm

137 ed macrophage-mediated phagocytosis of human SCLC patient cells in culture.

138 ly more growth regression and death of human SCLC xenografts in immunocompromised mice.

139 ations in NOTCH family genes in 25% of human SCLC.

140 ponding to transcriptional profiles of human SCLC.

141 ly 53 samples consisting of 36 primary human SCLC and normal tissue pairs and 17 matched SCLC and lym

142 herapy followed by relapse, similar to human SCLC.

143 Surgery is indicated for selected stage I SCLC.

144 In SCLC models in vitro and in vivo, LY2606368 exhibited st

145 an absence of nuclear staining for NKX2.2 in SCLC primary tumors was an independent predictor of impr

146 ratio [OR] = 2.44 in NSCLC and OR = 2.41 in SCLC; P < .001) but did not have an impact on the risk o

147 Although several molecular abnormalities in SCLC have been described, there are relatively few studi

148 identify a novel molecular network acting in SCLC linking autocrine BBS and Shh circuitries and sugge

149 e Hedgehog signaling pathway is activated in SCLC cells independently of the lung microenvironment.

150 xpression was abrogated by Notch activity in SCLC cells.

151 tegy to markedly improve ABT-263 activity in SCLC.

152 underwhelming activity as a single agent in SCLC patients.

153 ew of the spectrum of genomic alterations in SCLC and identify several potential targets for therapeu

154 nsive study of somatic genome alterations in SCLC uncovers several key biological processes and ident

155 important marker of CSC in other cancers, in SCLC cancer cells.

156 sistant CD133(+) cells with CSC character in SCLC, emphasizing its potential utility for improving th

157 peutic target to overcome chemoresistance in SCLC.

158 pressed cell-cycle checkpoint kinase CHK1 in SCLC.

159 ncreases Fas-induced apoptotic cell death in SCLC cells.

160 Aurora dependency in SCLC primarily involved Aurora B, required its kinase ac

161 ow Aurora kinase inhibitors are effective in SCLC cell lines bearing MYC amplification, which occur i

162 K1 inhibition may be especially effective in SCLC with MYC amplification or MYC protein overexpressio

163 Preliminary efficacy data are encouraging in SCLC.

164 identified 22 significantly mutated genes in SCLC, including genes encoding kinases, G protein-couple

165 identify a functional role for SOX genes in SCLC, particularly for SOX4 and several novel targets de

166 e also demonstrate that BBS activates Gli in SCLC cells, which is crucial for BBS-mediated SCLC proli

167 ght to identify novel mechanisms involved in SCLC chemoresistance.

168 expressed at significantly higher levels in SCLC, compared to lung adenocarcinoma.

169 BT-737 as a single agent is self-limiting in SCLC, but the addition of rapamycin can maintain or incr

170 itness a revolution of the same magnitude in SCLC treatment.

171 This study profiles DNA methylation in SCLC, patient-derived xenografts (PDX) and cell lines at

172 s of the SOX family of genes were mutated in SCLC.

173 Silencing of MYCL1 in SCLC cell lines that had the RLF-MYCL1 fusion decreased

174 elated with increased genomic copy number in SCLC lines.

175 ur suppressors TP53 and RB1 is obligatory in SCLC.

176 imaging oncogene receptors overexpressed in SCLC cells and can be an important basis for further con

177 s pathway, is significantly overexpressed in SCLC compared to non-small cell lung cancer.

178 nase CHK1, is significantly overexpressed in SCLC, compared to lung adenocarcinoma.

179 g tumor cells (CTCs), which are prevalent in SCLC, present a readily accessible 'liquid biopsy'.

180 ging initial safety and efficacy profiles in SCLC in the clinic.

181 with uncontrolled cell cycle progression in SCLC, we find that CDC25A, B and C mRNAs are expressed a

182 al leukocyte content was markedly reduced in SCLC compared with lung ADCA, which was validated in hum

183 Drug resistance in SCLC may be attributable to the persistence of a subpopu

184 ules in mediating chemotherapy resistance in SCLC.

185 se to initial chemotherapy, the responses in SCLC patients with metastatic disease are of short durat

186 ly amplified in human SCLC, but its roles in SCLC progression are poorly understood.

187 and pharmacological vulnerability screen in SCLC cell lines.

188 pression activates canonical Hh signaling in SCLC cells, and markedly accelerates tumor progression.

189 autocrine, ligand-dependent Hh signaling in SCLC has been disputed.

190 e, ligand-dependent model of Hh signaling in SCLC pathogenesis, and reveal a novel role for non-canon

191 in the DNA damage response, specifically in SCLC.

192 tone demethylase, as a therapeutic target in SCLC with a unique epigenetic signature to predict drug

193 elation for response to SC16LD6.5 therapy in SCLC patient-derived xenograft models.

194 b in phase 3 randomised controlled trials in SCLC.

195 topoisomerase II inhibitors commonly used in SCLC chemotherapy.

196 The functional significance of VM in SCLC suggests VM regulation may provide new targets for

197 al and neuroendocrine lung cancer, including SCLC.

198 in the lung epithelium of adult mice induces SCLC, we found that the Hedgehog signaling pathway is ac

199 Ganetespib inhibited SCLC cell growth via induction of persistent G2/M arrest

200 tivation of the Cd47 gene markedly inhibited SCLC tumor growth.

201 ant synergy and is efficacious in inhibiting SCLC growth in vitro and in mouse xenograft models.

202 cells in CTM may provide novel insights into SCLC biology.

203 are inoperable, and biopsies to investigate SCLC biology are rarely obtainable.

204 SCLC and normal tissue pairs and 17 matched SCLC and lymphoblastoid cell lines.

205 CLC cells, which is crucial for BBS-mediated SCLC proliferation, because cyclopamine, an inhibitor of

206 and non-neuroendocrine/mesenchymal-like (ML) SCLC phenotypes.

207 sis in an autochthonous Rb/p53-deleted mouse SCLC model and found significant tumor inhibition.

208 When compared to mouse SCLC tumors expressing an activating, ligand-independent

209 ro, as well as tumor regressions in multiple SCLC xenograft models.

210 engineered Pten deletion accelerated murine SCLC and abrogated loss of Chr19 in Trp53; Rb1; Pten com

211 xic damage and apoptosis in human and murine SCLC cell lines, but not in lung adenocarcinoma cells.

212 l and sequential metastatic spread of murine SCLC by comparative sequencing of families of related pr

213 ssor Pten occurred in the majority of murine SCLC studied, and engineered Pten deletion accelerated m

214 We further demonstrate that murine SCLC tumors were highly sensitive to ATR- and CHK1 inhib

215 sensitivity among patients with stage 1 non-SCLC patients in set 2 with 74% specificity, demonstrati

216 t 2, comparison of patients with stage 1 non-SCLC with asymptomatic age-matched smokers or individual

217 8% of small cell lung cancers (SCLC) and non-SCLC patients [receiver operator characteristic area und

218 ng MYC amplification, which occur in 3-7% of SCLC patients.

219 rograms and drives the metastatic ability of SCLC cells.

220 tumor behavior and the hypoxic adaptation of SCLC is poorly documented, we stained SCLC tumors arrang

221 nhibitors block the self-renewal capacity of SCLC cells, the lack of activating pathway mutations hav

222 thorough chemical and genomic exploration of SCLC cell lines may provide starting points for further

223 Our study suggests that a fraction of SCLC patients may benefit from therapeutic inhibition of

224 genetically engineered mouse model (GEMM) of SCLC initiated by loss of Trp53 and Rb1.

225 nished clonogenicity and malignant growth of SCLC cells in vivo Collectively, our studies validate th

226 One of the hallmarks of SCLC is its almost uniform chemotherapy sensitivity.

227 Although the incidence of SCLC decreased during each decade, the overall survival

228 naling in the development and maintenance of SCLC and identify Hedgehog pathway inhibition as a thera

229 arly detection and therapeutic management of SCLC.

230 c neuroendocrine cells from a mouse model of SCLC and found that ectopic expression of L-Myc, c-Myc,

231 We propose a temporal model of SCLC tumorigenesis with implications for human SCLC ther

232 letion genetically engineered mouse model of SCLC, the combination of ABT-263 and AZD8055 significant

233 a conditional Tp53;Rb1 mutant mouse model of SCLC, we now demonstrate a requirement for the Hh ligand

234 We also created mouse models of SCLC in which CGRP(CreER) was used to ablate multiple tu

235 Mycl in two genetically engineered models of SCLC resulted in strong suppression of SCLC.

236 ed patient-derived xenograft (PDX) models of SCLC to study ABT-737 resistance and demonstrated that r

237 The prognosis of SCLC patients is devastating and no biologically targete

238 Sonic Hedgehog (Shh) for the progression of SCLC.

239 s, the authors show exquisite sensitivity of SCLC to transcriptional inhibition.

240 The subset of SCLC lines and primary samples that undergo growth inhib

241 ves a neuroendocrine-low "variant" subset of SCLC with high NEUROD1 expression corresponding to trans

242 e a therapeutic target for a broad subset of SCLC.

243 ls of SCLC resulted in strong suppression of SCLC.

244 ssible therapeutic targets on the surface of SCLC cells.

245 The ACCP guideline on the treatment of SCLC was reviewed for developmental rigor by methodologi

246 d carboplatin in the first-line treatment of SCLC, but there are differences in the toxicity profile.

247 orses the ACCP guideline on the treatment of SCLC, with the addition of qualifying statements.

248 d delineation of subcutaneous and orthotopic SCLC tumor xenografts as well as distant organ metastase

249 In particular, SCLC cell lines possessed greater BIM transcript levels

250 ulating tumor cells (CTCs) from pretreatment SCLC blood samples.

251 of methylation changes that occur in primary SCLC and SCLC cell lines.

252 A methylation and gene expression of primary SCLC revealed distinct disease subtypes among histologic

253 nes capture the genomic landscape of primary SCLC tumors and provide genetic predictors for activity

254 rgets that are methylated in >77% of primary SCLC tumors, most of which have never been linked to abe

255 ty of patient tissues for research purposes, SCLC patient-derived xenografts (PDX) have provided the

256 PFS in patients who had platinum-refractory SCLC, but its addition increased toxicity.

257 num-sensitive or platinum-resistant relapsed SCLC.

258 family inhibition are observed in resistant SCLC transformed cancers compared with resistant NSCLCs.

259 However, a subset of relatively resistant SCLC cell lines has concomitant high expression of the a

260 of 637 patients with refractory or sensitive SCLC were randomly assigned at a ratio of 2:1 to 21-day

261 ts (testing set, 112 CTC samples) and in six SCLC patient-derived CTC explant tumors.

262 elop a framework for development of specific SCLC-targeted drugs we conducted a combined genomic and

263 -care for patients with cancer, specifically SCLC.

264 older, had limited-stage or extensive-stage SCLC, and had disease progression after at least one pre

265 was safe and improved PFS in extensive-stage SCLC.

266 ion of SCLC is poorly documented, we stained SCLC tumors arranged in a tissue microarray for hypoxia-

267 ion Pravastatin 40 mg combined with standard SCLC therapy, although safe, does not benefit patients.

268 HZ1 represents a prototype drug for tailored SCLC therapy.

269 fective pharmacological strategies to target SCLC biology represents an urgent need.

270 Altogether, our data indicate that SCLC displays an actionable dependence on ATR/CHK1-media

271 Our findings indicate that SCLC phenotypic heterogeneity can be specified dynamical

272 a diverse chemical library, we observe that SCLC is sensitive to transcription-targeting drugs, in p

273 Targeted drug screening reveals that SCLC with high MYC expression is vulnerable to Aurora ki

274 We show that SCLC cell lines capture the genomic landscape of primary

275 We show that SCLC patients (37/38) have rare CTC subpopulations co-ex

276 Here, we show that SCLC tumor samples feature co-expression of Shh and BBS-

277 Our findings suggest that SCLC can originate from differentiated PNECs.

278 We found that SCLCs were sensitized to ABT-263 via TORC1/2 inhibition,

279 The SCLC cohort of this phase 1/2 multicentre, multi-arm, op

280 ; here, we report an interim analysis of the SCLC cohort.

281 Retinoblastoma (RB) is lost in 100% of these SCLC transformed cases, but rarely in those that remain

282 The topology of this SCLC TF network was derived from prior knowledge and was

283 Thus, SCLC heterogeneity may be best understood as states with

284 ancers that transform from adenocarcinoma to SCLC.

285 anscription factors contributes, in part, to SCLC sensitivity to transcriptional inhibitors and that

286 transient and patients frequently succumb to SCLC within a year following diagnosis.

287 tumor progenitor cells to transition toward SCLC.

288 Patients with previously treated SCLC (one line of platinum-based chemotherapy), performa

289 Using SCLC cell lines, we demonstrated that ganetespib (IC50:

290 s modest but significant reduction of viable SCLC cells.

291 delay cancer recurrence in individuals with SCLC.

292 immunotherapeutic regimens in patients with SCLC and other cancers.

293 cidence of brain metastases in patients with SCLC and with non-metastatic NSCLC, but also improves ov

294 calculated survival changes in patients with SCLC during each decade between 1983 and 2012 to determi

295 Six serum samples from patients with SCLC were analyzed to demonstrate the methods feasibilit

296 In total, 106,296 patients with SCLC were identified, with the overall incidence per 100

297 d nivolumab plus ipilimumab in patients with SCLC who progressed after one or more previous regimens.

298 o improves overall survival in patients with SCLC who respond to first-line treatment.

299 profiles in previously treated patients with SCLC.

300 n the second-line treatment of patients with SCLC.