bigbio/hallmarks_of_cancer · Datasets at Hugging Face

id stringlengths 1 5	document_id stringlengths 9 11	text stringlengths 6 739	labels list
201	22313602_1	In this model , cancer cells secrete hydrogen peroxide ( H2O2 ) , initiating oxidative stress and aerobic glycolysis in the tumor stroma .	[ "none" ]
202	22313602_2	This , in turn , drives L-lactate secretion from cancer-associated fibroblasts .	[ "none" ]
203	22313602_3	Secreted L-lactate then fuels oxidative mitochondrial metabolism ( OXPHOS ) in epithelial cancer cells , by acting as a paracrine onco-metabolite .	[ "none" ]
204	22313602_4	We have previously termed this type of two-compartment tumor metabolism the " Reverse Warburg Effect, " as aerobic glycolysis takes place in stromal fibroblasts , rather than epithelial cancer cells .	[ "none" ]
205	22313602_5	Here , we used MCT4 immuno-staining of human breast cancer tissue microarrays ( TMAs ; > 180 triple-negative patients ) to directly assess the prognostic value of the " Reverse Warburg Effect. "	[ "none" ]
206	22313602_6	MCT4 expression is a functional marker of hypoxia , oxidative stress , aerobic glycolysis , and L-lactate efflux .	[ "none" ]
207	22313602_7	Remarkably , high stromal MCT4 levels ( score = 2 ) were specifically associated with decreased overall survival ( < 18% survival at 10 y post-diagnosis ) .	[ "none" ]
208	22313602_8	In contrast , patients with absent stromal MCT4 expression ( score = 0 ) , had 10-y survival rates of ( p-value < 10 ( -32 ) ) .	[ "none" ]
209	22313602_9	High stromal levels of MCT4 were strictly correlated with a loss of stromal Cav-1 ( p-value < 10 ( -14 ) ) , a known marker of early tumor recurrence and metastasis .	[ "none" ]
210	22313602_10	In fact , the combined use of stromal Cav-1 and stromal MCT4 allowed us to more precisely identify high-risk triple-negative breast cancer patients , consistent with the goal of individualized risk-assessment and personalized cancer treatment .	[ "none" ]
211	22313602_11	However , epithelial MCT4 staining had no prognostic value , indicating that the " conventional " Warburg effect does not predict clinical outcome .	[ "none" ]
212	22313602_12	Thus , the " Reverse Warburg Effect " or " parasitic " energy-transfer is a key determinant of poor overall patient survival .	[ "none" ]
213	22313602_13	As MCT4 is a druggable-target , MCT4 inhibitors should be developed for the treatment of aggressive breast cancers , and possibly other types of human cancers .	[ "none" ]
214	22313602_14	Similarly , we discuss how stromal MCT4 could be used as a biomarker for identifying high-risk cancer patients that could likely benefit from treatment with FDA-approved drugs or existing MCT-inhibitors ( such as , AR-C155858 , AR-C117977 , and AZD-3965 ) .	[ "none" ]
215	23143302_0	Mps one binder 1a ( MOB1A ) and MOB1B are key components of the Hippo signaling pathway and are mutated or inactivated in many human cancers .	[ "none" ]
216	23143302_1	Here we show that intact Mob1a or Mob1b is essential for murine embryogenesis and that loss of the remaining WT Mob1 allele in Mob1a(\u0394/\u0394)1b(tr/+) or Mob1a(\u0394/+)1b(tr/tr) mice results in tumor development .	[ "none" ]
217	23143302_2	Because most of these cancers resembled trichilemmal carcinomas , we generated double-mutant mice bearing tamoxifen-inducible , keratinocyte-specific homozygous-null mutations of Mob1a and Mob1b ( kDKO mice). kDKO mice showed hyperplastic keratinocyte progenitors and defective keratinocyte terminal differentiation and soon died of malnutrition. kDKO keratinocytes exhibited hyperproliferation , apoptotic resistance , impaired contact inhibition , enhanced progenitor self renewal , and increased centrosomes .	[ "resisting cell death", "sustaining proliferative signaling", "evading growth suppressors" ]
218	23143302_3	Examination of Hippo pathway signaling in kDKO keratinocytes revealed that loss of Mob1a/b altered the activities of the downstream Hippo mediators LATS and YAP1 .	[ "none" ]
219	23143302_4	Similarly , YAP1 was activated in some human trichilemmal carcinomas , and some of these also exhibited MOB1A/1B inactivation .	[ "none" ]
220	23143302_5	Our results clearly demonstrate that MOB1A and MOB1B have overlapping functions in skin homeostasis , and exert their roles as tumor suppressors by regulating downstream elements of the Hippo pathway .	[ "none" ]
221	22460537_0	OBJECTIVES/HYPOTHESIS Head and neck squamous cell carcinoma ( HNSCC ) is a complex disease process involving interactions with carcinoma-associated fibroblasts and endothelial cells .	[ "none" ]
222	22460537_1	We further investigated these relationships by suppressing stromal cell growth through the inhibition of fibroblast growth factor receptor ( FGFR ) .	[ "none" ]
223	22460537_2	STUDY DESIGN Preclinical investigation .	[ "none" ]
224	22460537_3	METHODS HNSCC cell lines ( FADU , OSC19 , Cal27 , SCC1 , SCC5 , SCC22A ) , fibroblast ( HS27 ) , and endothelial cells ( human umbilical vascular endothelial cell ) were cultured individually or in coculture .	[ "none" ]
225	22460537_4	Proliferation was assessed following treatment with a range of physiologic concentrations of FGFR inhibitor PD173074 .	[ "none" ]
226	22460537_5	Mice bearing established HNSCC xenografts were treated with PD173074 ( 12 mg/kg ) , and tumor histology was analyzed for stromal composition , proliferation ( Ki67 staining ) , and apoptosis ( TUNEL [ terminal deoxynucleotidyl transferase dUTP nick end labeling ] staining ) .	[ "none" ]
227	22460537_6	RESULTS In vitro , inhibition of FGFR with PD173074 dramatically reduced proliferation of fibroblasts and endothelial cells compared to untreated controls .	[ "none" ]
228	22460537_7	However , HNSCC cell proliferation was not affected by inhibition of FGFR .	[ "sustaining proliferative signaling" ]
229	22460537_8	When cocultured with fibroblasts , HNSCC cells proliferation increased by 15% to 80% ( P < .01 ) .	[ "sustaining proliferative signaling" ]
230	22460537_9	Furthermore , this fibroblast-enhanced tumor cell growth was suppressed by FGFR inhibition .	[ "sustaining proliferative signaling" ]
231	22460537_10	Additionally , treatment of mice bearing HNSCC xenografts with PD173074 resulted in significant growth inhibition ( P < .001 ) .	[ "none" ]
232	22460537_11	Additionally , those tumors from mice treated with PD173074 had a smaller stromal component , decreased proliferation , and increased apoptosis .	[ "resisting cell death", "sustaining proliferative signaling" ]
233	22460537_12	CONCLUSIONS Targeting the FGFR pathway in head and neck cancer acts through the stromal components to decrease HNSCC growth in vivo and in vitro .	[ "none" ]
234	23185620_0	There are contradictory observations about the different radiosensitivities of cancer stem cells and cancer non-stem cells .	[ "none" ]
235	23185620_1	To resolve these contradictory observations , we studied radiosensitivities by employing breast cancer stem cell ( CSC)-like MDA-MB231 and MDA-MB453 cells as well as their corresponding non-stem cells .	[ "none" ]
236	23185620_2	CSC-like cells proliferate without differentiating and have characteristics of tumor-initiating cells [ 1 ] .	[ "none" ]
237	23185620_3	These cells were exposed to \u03b3-rays ( 1.25-8.75 Gy ) and survival curves were determined by colony formation .	[ "none" ]
238	23185620_4	A final slope , D(0) , of the survival curve for each cell line was determined to measure radiosensitivity .	[ "none" ]
239	23185620_5	The D(0) of CSC-like and non-stem MDA-MB-453 cells were 1.16 Gy and 1.55 Gy , respectively .	[ "none" ]
240	23185620_6	Similar results were observed in MDA-MB-231 cells ( 0.94 Gy vs. 1.56 Gy ) .	[ "none" ]
241	23185620_7	After determination of radiosensitivity , we investigated intrinsic cellular determinants which influence radiosensitivity including cell cycle distribution , free-radical scavengers and DNA repair .	[ "none" ]
242	23185620_8	We observed that even though cell cycle status and antioxidant content may contribute to differential radiosensitivity , differential DNA repair capacity may be a greater determinant of radiosensitivity .	[ "genomic instability and mutation" ]
243	23185620_9	Unlike non-stem cells , CSC-like cells have little/no sublethal damage repair , a low intracellular level of ataxia telangiectasia mutated ( ATM ) and delay of \u03b3-H2AX foci removal ( DNA strand break repair ) .	[ "genomic instability and mutation" ]
244	23185620_10	These results suggest that low DNA repair capacity is responsible for the high radiosensitivity of these CSC-like cells .	[ "genomic instability and mutation" ]
245	12408370_0	Hormone replacement therapy , which is a common menopausal treatment , is contraindicated in women with breast cancers due to concerns regarding the potential for breast cell proliferation .	[ "none" ]
246	12408370_1	As such , there is a need for alternative methods for treating menopausal symptoms .	[ "none" ]
247	12408370_2	To determine the influence of one such alternative , black cohosh ( Cimicifuga racemosa [ CR] ) , on estrogen-dependent mammary cancers , we conducted an in vitro investigation of the effect of an isopropanolic CR-extract on the proliferation of estrogen receptor-positive breast cancer cells .	[ "none" ]
248	12408370_3	The experiments were performed using the human breast adenocarcinoma ( MCF-7 ) cell test system , an established in vitro model for estrogen-dependent tumors .	[ "none" ]
249	12408370_4	The influence of CR-extract on the proliferation of the MCF-7 cells was determined by measuring the incorporation of radioactively labeled thymidine .	[ "none" ]
250	12408370_5	Under estrogen-deprived conditions , the CR-extract ( 10(-3)-10(-5) dilutions ) significantly inhibited MCF-7 cell proliferation .	[ "sustaining proliferative signaling" ]
251	12408370_6	Additionally , application of the CR-extract inhibited estrogen-induced proliferation of MCF-7 cells .	[ "sustaining proliferative signaling" ]
252	12408370_7	Moreover , the proliferation-inhibiting effect of tamoxifen was enhanced by the CR-extract .	[ "sustaining proliferative signaling" ]
253	12408370_8	Such data that suggest a non-estrogenic , or estrogen-antagonistic effect of CR on human breast cancer cells lead to the conclusion that CR treatment may be a safe , natural remedy for menopausal symptoms in breast cancer .	[ "none" ]
254	12136428_0	We have recently developed surface-shielded transferrin-polyethylenimine ( Tf-PEI)/DNA delivery systems that target reporter gene expression to distant tumors after systemic application .	[ "none" ]
255	12136428_1	In the present study , we used surface-shielded Tf-PEI/DNA complexes for delivering the gene for a highly potent cytokine , tumor necrosis factor-alpha ( TNFalpha ) .	[ "none" ]
256	12136428_2	TNFalpha is known for its ability to induce hemorrhagic tumor necrosis and tumor regression .	[ "none" ]
257	12136428_3	However , the therapeutic application of TNFalpha is hampered by its high systemic toxicity dictating the need to target TNFalpha activity to the tumor .	[ "none" ]
258	12136428_4	Systemic application of surface-shielded Tf-PEI complexes with the TNFalpha gene resulted in preferential expression of TNFalpha in the tumor without detectable TNFalpha serum levels , in contrast to the application of nontargeted complexes .	[ "none" ]
259	12136428_5	Tumor-targeted TNFalpha gene delivery induced pronounced hemorrhagic tumor necrosis and inhibition of tumor growth in three murine tumor models of different tissue origins , Neuro2a neuroblastoma , MethA fibrosarcoma , and M-3 melanoma , with complete tumor regressions observed in the MethA model .	[ "resisting cell death" ]
260	12136428_6	No systemic TNF-related toxicity was observed due to the localization of the TNFalpha activity to the tumor .	[ "none" ]
261	12136428_7	Targeted gene therapy may be an attractive strategy applicable to highly active , yet toxic , molecules such as TNFalpha .	[ "none" ]
262	1281554_0	Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized by persistent angiogenesis .	[ "none" ]
263	1281554_1	The possibility was tested that interleukin-8 ( IL-8 ) , which is a cytokine that is chemotactic for lymphocytes and neutrophils , is also angiogenic .	[ "none" ]
264	1281554_2	Human recombinant IL-8 was potently angiogenic when implanted in the rat cornea and induced proliferation and chemotaxis of human umbilical vein endothelial cells .	[ "inducing angiogenesis" ]
265	1281554_3	Angiogenic activity present in the conditioned media of inflamed human rheumatoid synovial tissue macrophages or lipopolysaccharide-stimulated blood monocytes was equally blocked by antibodies to either IL-8 or tumor necrosis factor-alpha .	[ "inducing angiogenesis" ]
266	1281554_4	An IL-8 antisense oligonucleotide specifically blocked the production of monocyte-induced angiogenic activity .	[ "inducing angiogenesis" ]
267	1281554_5	These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis , tumor growth , and wound repair .	[ "inducing angiogenesis" ]
268	1282003_0	We have observed previously that treatment of plateau-phase L5178Y murine lymphoblasts in vitro with 2'-deoxycoformycin plus deoxyadenosine ( dCF/dAdo ) can inhibit the repair of X-irradiation-induced DNA single-strand breaks ( SSB ) in these cells and that this effect is associated with synergistic cell kill .	[ "none" ]
269	1282003_1	In this study we examined the effect of a combination treatment of plateau-phase L5178Y cells with bleomycin ( BLM ) plus dCF/dAdo .	[ "none" ]
270	1282003_2	Incubation of BLM-treated cells with dCF/dAdo resulted in significant inhibition of the repair of BLM-induced DNA SSB .	[ "genomic instability and mutation" ]
271	1282003_3	However , an additive , but not a synergistic , increase in cell kill was observed when cells were treated with a combination of BLM plus dCF/dAdo .	[ "resisting cell death" ]
272	22784709_0	Src kinase is elevated in breast tumors that are ER/PR negative and do not overexpress HER2 , but clinical trials with Src inhibitors have shown little activity .	[ "none" ]
273	22784709_1	The present study evaluated preclinical efficacy of a novel peptidomimetic compound , KX-01 ( KX2-391 ) , that exhibits dual action as an Src and pretubulin inhibitor .	[ "none" ]
274	22784709_2	KX-01 was evaluated as a single-agent and in combination with paclitaxel in MDA-MB-231 , MDA-MB-157 , and MDA-MB-468 human ER/PR/HER2-negative breast cancer cells .	[ "none" ]
275	22784709_3	Treatments were evaluated by growth/apoptosis , isobologram analysis , migration/invasion assays , tumor xenograft volume , metastasis , and measurement of Src , focal adhesion kinase ( FAK ) , microtubules , Ki67 , and microvessel density .	[ "none" ]
276	22784709_4	KX-01 inhibited cell growth in vitro and in combination with paclitaxel resulted in synergistic growth inhibition .	[ "none" ]
277	22784709_5	KX-01 resulted in a dose-dependent inhibition of MDA-MB-231 and MDA-MB-157 tumor xenografts ( 1 and 5 mg/kg , twice daily ) .	[ "none" ]
278	22784709_6	KX-01 inhibited activity of Src and downstream mediator FAK in tumors that was coincident with reduced proliferation and angiogenesis and increased apoptosis .	[ "resisting cell death", "sustaining proliferative signaling", "inducing angiogenesis" ]
279	22784709_7	KX01 also resulted in microtubule disruption in tumors .	[ "none" ]
280	22784709_8	Combination of KX-01 with paclitaxel resulted in significant regression of MDA-MB-231 tumors and reduced metastasis to mouse lung and liver .	[ "activating invasion and metastasis" ]
281	22784709_9	KX-01 is a potently active Src/pretubulin inhibitor that inhibits breast tumor growth and metastasis .	[ "activating invasion and metastasis" ]
282	22784709_10	As ER/PR/HER2-negative patients are candidates for paclitaxel therapy , combination with KX-01 may potentiate antitumor efficacy in management of this aggressive breast cancer subtype .	[ "none" ]
283	20658731_0	PURPOSE Overproduction of reactive oxygen species ( ROS ) intermediates above the functional capability of cellular antioxidants may result in instability of important macromolecules and represents the molecular basis of many diseases including inflammation processes , cardiovascular alterations , cancer etc .	[ "none" ]
284	20658731_1	The purpose of this study was to determine plasma level of superoxide anion , hydrogen-peroxide and malondialdehyde ( MDA ) as markers of oxidative stress and activities of superoxide dismutase ( SOD ) , catalase ( CAT ) and glutathione peroxidase ( GPx ) as antioxidant enzymes in B-chronic lymphocytic leukemia ( B-CLL ) patients .	[ "none" ]
285	20658731_2	METHODS The study included 29 untreated B-CLL patients in stage A , and 21 in stages B and C , classified according to the Binet system ; 31 healthy volunteers formed the control group .	[ "none" ]
286	20658731_3	After centrifugation of heparinized peripheral blood , plasma levels of all investigated parameters were determined using spectrophotometric methods .	[ "none" ]
287	20658731_4	RESULTS Plasma CAT activity was increased in B-CLL patients compared with control subjects ; also , progression of disease was related with significantly higher plasma activity of CAT .	[ "tumor promoting inflammation" ]
288	20658731_5	Also , B-CLL patients showed significantly higher plasma concentration of MDA compared with controls .	[ "none" ]
289	20658731_6	No statistically significant differences of superoxide anion and hydrogen peroxide as well as plasma activity of SOD and GPx between the tested groups were noted .	[ "tumor promoting inflammation" ]
290	20658731_7	CONCLUSION Increase of CAT activity in B-CLL patients indicates that there is stimulation of the antioxidant enzyme system , while the increase of MDA concentration shows increased lipid peroxidation level .	[ "tumor promoting inflammation" ]
291	20658731_8	According to these results it could be concluded that an imbalance exists between oxidants and antioxidants in the plasma of B-CLL patients .	[ "tumor promoting inflammation" ]
292	22431001_0	Identification of molecular target(s) and mechanism(s) of silica-induced pulmonary toxicity is important for the intervention and/or prevention of diseases associated with exposure to silica .	[ "none" ]
293	22431001_1	Rats were exposed to crystalline silica by inhalation ( 15 mg m(-3) , 6 h per day , 5 days ) and global gene expression profile was determined in the lungs by microarray analysis at 1 , 2 , 4 , 8 and 16 weeks following termination of silica exposure .	[ "none" ]
294	22431001_2	The number of significantly differentially expressed genes ( >1.5-fold change and <0.01 false discovery rate P-value ) detected in the lungs during the post-exposure time intervals analyzed exhibited a steady increase in parallel with the progression of silica-induced pulmonary toxicity noticed in the rats .	[ "none" ]
295	22431001_3	Quantitative real-time PCR analysis of a representative set of 10 genes confirmed the microarray findings .	[ "none" ]
296	22431001_4	The number of biological functions , canonical pathways and molecular networks significantly affected by silica exposure , as identified by the bioinformatics analysis of the significantly differentially expressed genes detected during the post-exposure time intervals , also exhibited a steady increase similar to the silica-induced pulmonary toxicity .	[ "none" ]
297	22431001_5	Genes involved in oxidative stress , inflammation , respiratory diseases , cancer , and tissue remodeling and fibrosis were significantly differentially expressed in the rat lungs ; however , unresolved inflammation was the single most significant biological response to pulmonary exposure to silica .	[ "tumor promoting inflammation" ]
298	22431001_6	Excessive mucus production , as implicated by significant overexpression of the pendrin coding gene , SLC26A4 , was identified as a potential novel mechanism for silica-induced pulmonary toxicity .	[ "none" ]
299	22431001_7	Collectively , the findings of our study provided insights into the molecular mechanisms underlying the progression of crystalline silica-induced pulmonary toxicity in the rat .	[ "none" ]
300	22431001_8	Published 2012 .	[ "none" ]

201

22313602_1

In this model , cancer cells secrete hydrogen peroxide ( H2O2 ) , initiating oxidative stress and aerobic glycolysis in the tumor stroma .

[ "none" ]

202

22313602_2

This , in turn , drives L-lactate secretion from cancer-associated fibroblasts .

[ "none" ]

203

22313602_3

Secreted L-lactate then fuels oxidative mitochondrial metabolism ( OXPHOS ) in epithelial cancer cells , by acting as a paracrine onco-metabolite .

[ "none" ]

204

22313602_4

We have previously termed this type of two-compartment tumor metabolism the " Reverse Warburg Effect, " as aerobic glycolysis takes place in stromal fibroblasts , rather than epithelial cancer cells .

[ "none" ]

205

22313602_5

Here , we used MCT4 immuno-staining of human breast cancer tissue microarrays ( TMAs ; > 180 triple-negative patients ) to directly assess the prognostic value of the " Reverse Warburg Effect. "

[ "none" ]

206

22313602_6

MCT4 expression is a functional marker of hypoxia , oxidative stress , aerobic glycolysis , and L-lactate efflux .

[ "none" ]

207

22313602_7

Remarkably , high stromal MCT4 levels ( score = 2 ) were specifically associated with decreased overall survival ( < 18% survival at 10 y post-diagnosis ) .

[ "none" ]

208

22313602_8

In contrast , patients with absent stromal MCT4 expression ( score = 0 ) , had 10-y survival rates of ( p-value < 10 ( -32 ) ) .

[ "none" ]

209

22313602_9

High stromal levels of MCT4 were strictly correlated with a loss of stromal Cav-1 ( p-value < 10 ( -14 ) ) , a known marker of early tumor recurrence and metastasis .

[ "none" ]

210

22313602_10

In fact , the combined use of stromal Cav-1 and stromal MCT4 allowed us to more precisely identify high-risk triple-negative breast cancer patients , consistent with the goal of individualized risk-assessment and personalized cancer treatment .

[ "none" ]

211

22313602_11

However , epithelial MCT4 staining had no prognostic value , indicating that the " conventional " Warburg effect does not predict clinical outcome .

[ "none" ]

212

22313602_12

Thus , the " Reverse Warburg Effect " or " parasitic " energy-transfer is a key determinant of poor overall patient survival .

[ "none" ]

213

22313602_13

As MCT4 is a druggable-target , MCT4 inhibitors should be developed for the treatment of aggressive breast cancers , and possibly other types of human cancers .

[ "none" ]

214

22313602_14

Similarly , we discuss how stromal MCT4 could be used as a biomarker for identifying high-risk cancer patients that could likely benefit from treatment with FDA-approved drugs or existing MCT-inhibitors ( such as , AR-C155858 , AR-C117977 , and AZD-3965 ) .

[ "none" ]

215

23143302_0

Mps one binder 1a ( MOB1A ) and MOB1B are key components of the Hippo signaling pathway and are mutated or inactivated in many human cancers .

[ "none" ]

216

23143302_1

Here we show that intact Mob1a or Mob1b is essential for murine embryogenesis and that loss of the remaining WT Mob1 allele in Mob1a(\u0394/\u0394)1b(tr/+) or Mob1a(\u0394/+)1b(tr/tr) mice results in tumor development .

[ "none" ]

217

23143302_2

Because most of these cancers resembled trichilemmal carcinomas , we generated double-mutant mice bearing tamoxifen-inducible , keratinocyte-specific homozygous-null mutations of Mob1a and Mob1b ( kDKO mice). kDKO mice showed hyperplastic keratinocyte progenitors and defective keratinocyte terminal differentiation and soon died of malnutrition. kDKO keratinocytes exhibited hyperproliferation , apoptotic resistance , impaired contact inhibition , enhanced progenitor self renewal , and increased centrosomes .

[ "resisting cell death", "sustaining proliferative signaling", "evading growth suppressors" ]

218

23143302_3

Examination of Hippo pathway signaling in kDKO keratinocytes revealed that loss of Mob1a/b altered the activities of the downstream Hippo mediators LATS and YAP1 .

[ "none" ]

219

23143302_4

Similarly , YAP1 was activated in some human trichilemmal carcinomas , and some of these also exhibited MOB1A/1B inactivation .

[ "none" ]

220

23143302_5

Our results clearly demonstrate that MOB1A and MOB1B have overlapping functions in skin homeostasis , and exert their roles as tumor suppressors by regulating downstream elements of the Hippo pathway .

[ "none" ]

221

22460537_0

OBJECTIVES/HYPOTHESIS Head and neck squamous cell carcinoma ( HNSCC ) is a complex disease process involving interactions with carcinoma-associated fibroblasts and endothelial cells .

[ "none" ]

222

22460537_1

We further investigated these relationships by suppressing stromal cell growth through the inhibition of fibroblast growth factor receptor ( FGFR ) .

[ "none" ]

223

22460537_2

STUDY DESIGN Preclinical investigation .

[ "none" ]

224

22460537_3

METHODS HNSCC cell lines ( FADU , OSC19 , Cal27 , SCC1 , SCC5 , SCC22A ) , fibroblast ( HS27 ) , and endothelial cells ( human umbilical vascular endothelial cell ) were cultured individually or in coculture .

[ "none" ]

225

22460537_4

Proliferation was assessed following treatment with a range of physiologic concentrations of FGFR inhibitor PD173074 .

[ "none" ]

226

22460537_5

Mice bearing established HNSCC xenografts were treated with PD173074 ( 12 mg/kg ) , and tumor histology was analyzed for stromal composition , proliferation ( Ki67 staining ) , and apoptosis ( TUNEL [ terminal deoxynucleotidyl transferase dUTP nick end labeling ] staining ) .

[ "none" ]

227

22460537_6

RESULTS In vitro , inhibition of FGFR with PD173074 dramatically reduced proliferation of fibroblasts and endothelial cells compared to untreated controls .

[ "none" ]

228

22460537_7

However , HNSCC cell proliferation was not affected by inhibition of FGFR .

[ "sustaining proliferative signaling" ]

229

22460537_8

When cocultured with fibroblasts , HNSCC cells proliferation increased by 15% to 80% ( P < .01 ) .

[ "sustaining proliferative signaling" ]

230

22460537_9

Furthermore , this fibroblast-enhanced tumor cell growth was suppressed by FGFR inhibition .

[ "sustaining proliferative signaling" ]

231

22460537_10

Additionally , treatment of mice bearing HNSCC xenografts with PD173074 resulted in significant growth inhibition ( P < .001 ) .

[ "none" ]

232

22460537_11

Additionally , those tumors from mice treated with PD173074 had a smaller stromal component , decreased proliferation , and increased apoptosis .

[ "resisting cell death", "sustaining proliferative signaling" ]

233

22460537_12

CONCLUSIONS Targeting the FGFR pathway in head and neck cancer acts through the stromal components to decrease HNSCC growth in vivo and in vitro .

[ "none" ]

234

23185620_0

There are contradictory observations about the different radiosensitivities of cancer stem cells and cancer non-stem cells .

[ "none" ]

235

23185620_1

To resolve these contradictory observations , we studied radiosensitivities by employing breast cancer stem cell ( CSC)-like MDA-MB231 and MDA-MB453 cells as well as their corresponding non-stem cells .

[ "none" ]

236

23185620_2

CSC-like cells proliferate without differentiating and have characteristics of tumor-initiating cells [ 1 ] .

[ "none" ]

237

23185620_3

These cells were exposed to \u03b3-rays ( 1.25-8.75 Gy ) and survival curves were determined by colony formation .

[ "none" ]

238

23185620_4

A final slope , D(0) , of the survival curve for each cell line was determined to measure radiosensitivity .

[ "none" ]

239

23185620_5

The D(0) of CSC-like and non-stem MDA-MB-453 cells were 1.16 Gy and 1.55 Gy , respectively .

[ "none" ]

240

23185620_6

Similar results were observed in MDA-MB-231 cells ( 0.94 Gy vs. 1.56 Gy ) .

[ "none" ]

241

23185620_7

After determination of radiosensitivity , we investigated intrinsic cellular determinants which influence radiosensitivity including cell cycle distribution , free-radical scavengers and DNA repair .

[ "none" ]

242

23185620_8

We observed that even though cell cycle status and antioxidant content may contribute to differential radiosensitivity , differential DNA repair capacity may be a greater determinant of radiosensitivity .

[ "genomic instability and mutation" ]

243

23185620_9

Unlike non-stem cells , CSC-like cells have little/no sublethal damage repair , a low intracellular level of ataxia telangiectasia mutated ( ATM ) and delay of \u03b3-H2AX foci removal ( DNA strand break repair ) .

[ "genomic instability and mutation" ]

244

23185620_10

These results suggest that low DNA repair capacity is responsible for the high radiosensitivity of these CSC-like cells .

[ "genomic instability and mutation" ]

245

12408370_0

Hormone replacement therapy , which is a common menopausal treatment , is contraindicated in women with breast cancers due to concerns regarding the potential for breast cell proliferation .

[ "none" ]

246

12408370_1

As such , there is a need for alternative methods for treating menopausal symptoms .

[ "none" ]

247

12408370_2

To determine the influence of one such alternative , black cohosh ( Cimicifuga racemosa [ CR] ) , on estrogen-dependent mammary cancers , we conducted an in vitro investigation of the effect of an isopropanolic CR-extract on the proliferation of estrogen receptor-positive breast cancer cells .

[ "none" ]

248

12408370_3

The experiments were performed using the human breast adenocarcinoma ( MCF-7 ) cell test system , an established in vitro model for estrogen-dependent tumors .

[ "none" ]

249

12408370_4

The influence of CR-extract on the proliferation of the MCF-7 cells was determined by measuring the incorporation of radioactively labeled thymidine .

[ "none" ]

250

12408370_5

Under estrogen-deprived conditions , the CR-extract ( 10(-3)-10(-5) dilutions ) significantly inhibited MCF-7 cell proliferation .

[ "sustaining proliferative signaling" ]

251

12408370_6

Additionally , application of the CR-extract inhibited estrogen-induced proliferation of MCF-7 cells .

[ "sustaining proliferative signaling" ]

252

12408370_7

Moreover , the proliferation-inhibiting effect of tamoxifen was enhanced by the CR-extract .

[ "sustaining proliferative signaling" ]

253

12408370_8

Such data that suggest a non-estrogenic , or estrogen-antagonistic effect of CR on human breast cancer cells lead to the conclusion that CR treatment may be a safe , natural remedy for menopausal symptoms in breast cancer .

[ "none" ]

254

12136428_0

We have recently developed surface-shielded transferrin-polyethylenimine ( Tf-PEI)/DNA delivery systems that target reporter gene expression to distant tumors after systemic application .

[ "none" ]

255

12136428_1

In the present study , we used surface-shielded Tf-PEI/DNA complexes for delivering the gene for a highly potent cytokine , tumor necrosis factor-alpha ( TNFalpha ) .

[ "none" ]

256

12136428_2

TNFalpha is known for its ability to induce hemorrhagic tumor necrosis and tumor regression .

[ "none" ]

257

12136428_3

However , the therapeutic application of TNFalpha is hampered by its high systemic toxicity dictating the need to target TNFalpha activity to the tumor .

[ "none" ]

258

12136428_4

Systemic application of surface-shielded Tf-PEI complexes with the TNFalpha gene resulted in preferential expression of TNFalpha in the tumor without detectable TNFalpha serum levels , in contrast to the application of nontargeted complexes .

[ "none" ]

259

12136428_5

Tumor-targeted TNFalpha gene delivery induced pronounced hemorrhagic tumor necrosis and inhibition of tumor growth in three murine tumor models of different tissue origins , Neuro2a neuroblastoma , MethA fibrosarcoma , and M-3 melanoma , with complete tumor regressions observed in the MethA model .

[ "resisting cell death" ]

260

12136428_6

No systemic TNF-related toxicity was observed due to the localization of the TNFalpha activity to the tumor .

[ "none" ]

261

12136428_7

Targeted gene therapy may be an attractive strategy applicable to highly active , yet toxic , molecules such as TNFalpha .

[ "none" ]

262

1281554_0

Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized by persistent angiogenesis .

[ "none" ]

263

1281554_1

The possibility was tested that interleukin-8 ( IL-8 ) , which is a cytokine that is chemotactic for lymphocytes and neutrophils , is also angiogenic .

[ "none" ]

264

1281554_2

Human recombinant IL-8 was potently angiogenic when implanted in the rat cornea and induced proliferation and chemotaxis of human umbilical vein endothelial cells .

[ "inducing angiogenesis" ]

265

1281554_3

Angiogenic activity present in the conditioned media of inflamed human rheumatoid synovial tissue macrophages or lipopolysaccharide-stimulated blood monocytes was equally blocked by antibodies to either IL-8 or tumor necrosis factor-alpha .

[ "inducing angiogenesis" ]

266

1281554_4

An IL-8 antisense oligonucleotide specifically blocked the production of monocyte-induced angiogenic activity .

[ "inducing angiogenesis" ]

267

1281554_5

These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis , tumor growth , and wound repair .

[ "inducing angiogenesis" ]

268

1282003_0

We have observed previously that treatment of plateau-phase L5178Y murine lymphoblasts in vitro with 2'-deoxycoformycin plus deoxyadenosine ( dCF/dAdo ) can inhibit the repair of X-irradiation-induced DNA single-strand breaks ( SSB ) in these cells and that this effect is associated with synergistic cell kill .

[ "none" ]

269

1282003_1

In this study we examined the effect of a combination treatment of plateau-phase L5178Y cells with bleomycin ( BLM ) plus dCF/dAdo .

[ "none" ]

270

1282003_2

Incubation of BLM-treated cells with dCF/dAdo resulted in significant inhibition of the repair of BLM-induced DNA SSB .

[ "genomic instability and mutation" ]

271

1282003_3

However , an additive , but not a synergistic , increase in cell kill was observed when cells were treated with a combination of BLM plus dCF/dAdo .

[ "resisting cell death" ]

272

22784709_0

Src kinase is elevated in breast tumors that are ER/PR negative and do not overexpress HER2 , but clinical trials with Src inhibitors have shown little activity .

[ "none" ]

273

22784709_1

The present study evaluated preclinical efficacy of a novel peptidomimetic compound , KX-01 ( KX2-391 ) , that exhibits dual action as an Src and pretubulin inhibitor .

[ "none" ]

274

22784709_2

KX-01 was evaluated as a single-agent and in combination with paclitaxel in MDA-MB-231 , MDA-MB-157 , and MDA-MB-468 human ER/PR/HER2-negative breast cancer cells .

[ "none" ]

275

22784709_3

Treatments were evaluated by growth/apoptosis , isobologram analysis , migration/invasion assays , tumor xenograft volume , metastasis , and measurement of Src , focal adhesion kinase ( FAK ) , microtubules , Ki67 , and microvessel density .

[ "none" ]

276

22784709_4

KX-01 inhibited cell growth in vitro and in combination with paclitaxel resulted in synergistic growth inhibition .

[ "none" ]

277

22784709_5

KX-01 resulted in a dose-dependent inhibition of MDA-MB-231 and MDA-MB-157 tumor xenografts ( 1 and 5 mg/kg , twice daily ) .

[ "none" ]

278

22784709_6

KX-01 inhibited activity of Src and downstream mediator FAK in tumors that was coincident with reduced proliferation and angiogenesis and increased apoptosis .

[ "resisting cell death", "sustaining proliferative signaling", "inducing angiogenesis" ]

279

22784709_7

KX01 also resulted in microtubule disruption in tumors .

[ "none" ]

280

22784709_8

Combination of KX-01 with paclitaxel resulted in significant regression of MDA-MB-231 tumors and reduced metastasis to mouse lung and liver .

[ "activating invasion and metastasis" ]

281

22784709_9

KX-01 is a potently active Src/pretubulin inhibitor that inhibits breast tumor growth and metastasis .

[ "activating invasion and metastasis" ]

282

22784709_10

As ER/PR/HER2-negative patients are candidates for paclitaxel therapy , combination with KX-01 may potentiate antitumor efficacy in management of this aggressive breast cancer subtype .

[ "none" ]

283

20658731_0

PURPOSE Overproduction of reactive oxygen species ( ROS ) intermediates above the functional capability of cellular antioxidants may result in instability of important macromolecules and represents the molecular basis of many diseases including inflammation processes , cardiovascular alterations , cancer etc .

[ "none" ]

284

20658731_1

The purpose of this study was to determine plasma level of superoxide anion , hydrogen-peroxide and malondialdehyde ( MDA ) as markers of oxidative stress and activities of superoxide dismutase ( SOD ) , catalase ( CAT ) and glutathione peroxidase ( GPx ) as antioxidant enzymes in B-chronic lymphocytic leukemia ( B-CLL ) patients .

[ "none" ]

285

20658731_2

METHODS The study included 29 untreated B-CLL patients in stage A , and 21 in stages B and C , classified according to the Binet system ; 31 healthy volunteers formed the control group .

[ "none" ]

286

20658731_3

After centrifugation of heparinized peripheral blood , plasma levels of all investigated parameters were determined using spectrophotometric methods .

[ "none" ]

287

20658731_4

RESULTS Plasma CAT activity was increased in B-CLL patients compared with control subjects ; also , progression of disease was related with significantly higher plasma activity of CAT .

[ "tumor promoting inflammation" ]

288

20658731_5

Also , B-CLL patients showed significantly higher plasma concentration of MDA compared with controls .

[ "none" ]

289

20658731_6

No statistically significant differences of superoxide anion and hydrogen peroxide as well as plasma activity of SOD and GPx between the tested groups were noted .

[ "tumor promoting inflammation" ]

290

20658731_7

CONCLUSION Increase of CAT activity in B-CLL patients indicates that there is stimulation of the antioxidant enzyme system , while the increase of MDA concentration shows increased lipid peroxidation level .

[ "tumor promoting inflammation" ]

291

20658731_8

According to these results it could be concluded that an imbalance exists between oxidants and antioxidants in the plasma of B-CLL patients .

[ "tumor promoting inflammation" ]

292

22431001_0

Identification of molecular target(s) and mechanism(s) of silica-induced pulmonary toxicity is important for the intervention and/or prevention of diseases associated with exposure to silica .

[ "none" ]

293

22431001_1

Rats were exposed to crystalline silica by inhalation ( 15 mg m(-3) , 6 h per day , 5 days ) and global gene expression profile was determined in the lungs by microarray analysis at 1 , 2 , 4 , 8 and 16 weeks following termination of silica exposure .

[ "none" ]

294

22431001_2

The number of significantly differentially expressed genes ( >1.5-fold change and <0.01 false discovery rate P-value ) detected in the lungs during the post-exposure time intervals analyzed exhibited a steady increase in parallel with the progression of silica-induced pulmonary toxicity noticed in the rats .

[ "none" ]

295

22431001_3

Quantitative real-time PCR analysis of a representative set of 10 genes confirmed the microarray findings .

[ "none" ]

296

22431001_4

The number of biological functions , canonical pathways and molecular networks significantly affected by silica exposure , as identified by the bioinformatics analysis of the significantly differentially expressed genes detected during the post-exposure time intervals , also exhibited a steady increase similar to the silica-induced pulmonary toxicity .

[ "none" ]

297

22431001_5

Genes involved in oxidative stress , inflammation , respiratory diseases , cancer , and tissue remodeling and fibrosis were significantly differentially expressed in the rat lungs ; however , unresolved inflammation was the single most significant biological response to pulmonary exposure to silica .

[ "tumor promoting inflammation" ]

298

22431001_6

Excessive mucus production , as implicated by significant overexpression of the pendrin coding gene , SLC26A4 , was identified as a potential novel mechanism for silica-induced pulmonary toxicity .

[ "none" ]

299

22431001_7

Collectively , the findings of our study provided insights into the molecular mechanisms underlying the progression of crystalline silica-induced pulmonary toxicity in the rat .

[ "none" ]

300

22431001_8

Published 2012 .

[ "none" ]