ライフサイエンスコーパス: tumor tissue

1 ion in the interstitial space throughout the tumor tissue.

2 10% to 22% of the injected dose per gram of tumor tissue.

3 umor cell surface in viable EpCAM-expressing tumor tissue.

4 smic area of cancer cells that comprised the tumor tissue.

5 tivity in eight cell lines and in colorectal tumor tissue.

6 o immunotherapy both in the periphery and in tumor tissue.

7 te leaky tumor vessels and accumulate in the tumor tissue.

8 largely unknown because of limited access to tumor tissue.

9 and BRAF mutations were assessed in archival tumor tissue.

10 nanoparticles preferentially accumulated in tumor tissue.

11 n is assessed by in vitro assays on biopsied tumor tissue.

12 ine the accuracy of FNA procedures to sample tumor tissue.

13 4)Cu-NOTA-FVIIai was colocalized with viable tumor tissue.

14 circulation of the drug and accumulation in tumor tissue.

15 t the reprogrammed AR binding sites in human tumor tissue.

16 he phosphorylation of both RET and VEGFR2 in tumor tissue.

17 irectly applied to irradiate cancer cells or tumor tissue.

18 19 deletion or L858R mutation in exon 21) in tumor tissue.

19 ith heterogeneous distribution of the viable tumor tissue.

20 photosensitizers accumulated selectively in tumor tissue.

21 ls that constitute the organ, as well as the tumor tissue.

22 is designed to discriminate between self and tumor tissue.

23 vitro in tumor cells and in vivo but only in tumor tissue.

24 according to the presence of F nucleatum in tumor tissue.

25 cient delivery of chemotherapeutic agents to tumor tissue.

26 umor penetration and uptake by cells in deep tumor tissue.

27 rates mimicking the stiffness of healthy and tumor tissue.

28 efficient retention of both therapeutics in tumor tissue.

29 ermia can improve nanoparticle delivery into tumor tissue.

30 vide information about glucose metabolism in tumor tissue.

31 upplemented immunohistochemistry of biopsied tumor tissue.

32 as calcium content endured at high levels in tumor tissue.

33 d with diminished MYC expression in residual tumor tissues.

34 stabilizes insoluble collagen deposition in tumor tissues.

35 and HO-1 and reduced blood vessel density in tumor tissues.

36 ing quantitative proteomic analysis in mouse tumor tissues.

37 ere detected in colon tumor and adjacent non-tumor tissues.

38 infiltration, distribution, and function in tumor tissues.

39 various osteosarcoma cell lines and patient tumor tissues.

40 C cells and was drastically downregulated in tumor tissues.

41 n of CD4(+) but not CD8(+) cells to xenogaft tumor tissues.

42 ellular carcinoma (PHC) tissues than in peri-tumor tissues.

43 r robust biological bone, breast, cardiac or tumor tissues.

44 ctively shrinking the hypoxic regions in the tumor tissues.

45 uman normal liver and lung as well as paired tumor tissues.

46 tivation of STAT3 in multiple types of human tumor tissues.

47 was also higher in PHC tissues than in peri-tumor tissues.

48 t cold plasma irradiation on cancer cells or tumor tissues.

49 carriers with self-sufficing H2O2 stimuli in tumor tissues.

50 own to localize/accumulate preferentially in tumor tissues.

51 d through comparing tumors with adjacent non-tumor tissues.

52 that did not overexpress this gene, and non-tumor tissues.

53 otic translation initiation factor 4E in the tumor tissues.

54 astric tissues, single-sorted stem cells, or tumor tissues.

55 viding an excellent match to DOX kinetics in tumor tissues.

56 inhibited stromal cell infiltration into the tumor tissues.

57 e lack of CAR that is frequently observed in tumor tissues.

58 NFE2L2-mediated genes that were enriched in tumor tissues.

59 NEDD4 levels was observed in prostate cancer tumor tissues.

60 cancer cells rather than in stromal cells of tumor tissues.

61 related with the expression of CYP2C9 in HCC tumor tissues.

62 ost active promoter of vasopermeation in non-tumor tissues.

63 d immunohistochemically in paraffin-embedded tumor tissues.

64 ch studies of morphologic characteristics of tumor tissues.

65 s and increased infiltration of T cells into tumor tissues.

66 in melanoma, in both cell lines and patient tumor tissues.

67 in both CS cell lines (CS-1 and SW1353) and tumor tissues.

68 y correlated with the upregulation of KIT in tumor tissues.

69 ressed in various skin cancer cell lines and tumor tissues.

70 expression of NOTCH ligands and receptors in tumor tissues.

71 ion was evaluated in human prostate archival tumor tissues.

72 FDG revealed a similar distribution in vital tumor tissue 1 h after injection.

73 ntly and resulted in selective and efficient tumor tissue ablation in the rabbit model.

74 reduced expression of Ki-67 and survivin in tumor tissues accompanied the observed effects.

75 vated during blood circulation for efficient tumor tissue accumulation, but re-activated by certain i

76 veness, shows good potential to enhance both tumor tissue accumulation/retention and cellular interna

77 rticles for targeted delivery, both enhanced tumor tissue accumulation/retention and enhanced cellula

78 The inefficient vascularization of tumor tissue also limits the penetration of other serum-

79 the tracer had the ability to be retained in tumor tissue and bind to PARP-1 with specificity.

80 ood circulation, lack of active targeting to tumor tissue and cells, and poor tissue penetration.

81 and its relationship with TSPO expression in tumor tissue and glioma-associated microglia/macrophages

82 achieve uniform and broad dispersion within tumor tissue and highlight the utility of SPR as a high

83 s of how to relate fluorescence intensity to tumor tissue and how to quantitatively assign a normaliz

84 ted that the plasma induces apoptosis in the tumor tissue and increases the ratio of the apoptotic to

85 y to efficiently retain both therapeutics in tumor tissue and induce a potent antitumor immune respon

86 tumor or MDA-MB-231 cells than in distal non-tumor tissue and low-metastatic MCF-7 cells, respectivel

87 mponent of AITL, and that 2HG is elevated in tumor tissue and serum of patients.

88 Actionable contrast was achieved between tumor tissue and surrounding normal tissues in adenocarc

89 allenging due to the heterogeneous nature of tumor tissue and the unintended induction of muscle cont

90 ning homeostasis, distinguishing normal from tumor tissue and trigger autoimmune diseases.

91 Tumor tissue and tumor-associated stroma showed evident

92 analyses of (a) TAM-abundant and -deficient tumor tissues and (b) sorted tumor-associated and -resid

93 A total of 28 articles including 2,171 tumor tissues and 1,191 controls were involved in the me

94 on of the selected lncRNAs in a cohort of 42 tumor tissues and adjacent normal tissues.

95 DNA was isolated from tumor tissues and analyzed by quantitative polymerase ch

96 t CDK11(p110) was highly expressed in breast tumor tissues and cell lines.

97 levels of B7-H4 expression found in numerous tumor tissues and correlation of the level of expression

98 targeted delivery of photothermal agents to tumor tissues and enhance the PTT effect.

99 ning the expression of CDK11(p110) in breast tumor tissues and examining the phenotypic changes of br

100 By polyribosome profiling of tumor tissues and human breast cancer cells, we observe

101 d HLA class-I expression was observed in MCC tumor tissues and MCC cell lines.

102 FC signaling and lymphatic barriers in human tumor tissues and mice with orthotopic colorectal tumors

103 sistently, hCDC14A is down-regulated in many tumor tissues and reduced hCDC14A expression is correlat

104 e sarcoma viral oncogene homolog B (BRAF) in tumor tissues and significantly suppresses tumor growth

105 llowing for discrimination between different tumor tissues and subtypes, even after long-term expansi

106 significantly overexpressed in human breast tumor tissues and were associated with reduced overall p

107 ologist to differentiate healthy tissue from tumor tissue, and basic tissue culture skills.

108 normal samples, MFI2-AS1 was upregulated in tumor tissue, and higher expression was associated with

109 o mitochondria in cancer cell lines, ex vivo tumor tissue, and mouse embryonic fibroblasts (MEFs).

110 iR-21 and FBXO11 are inversely correlated in tumor tissue, and their expression correlates with patie

111 HuR expression is consistently elevated in tumor tissues, and a cytoplasmic localization appears es

112 ant patient-derived xenograft model, patient tumor tissues, and genome-wide transcription and transla

113 e widespread expression in epithelial cells, tumor tissues, and macrophages detected using BTN3A anti

114 , NLRC4, NLRP6, NRLP12, and AIM2 in prostate tumor tissues, and verified their mRNA level in a panel

115 Tumor tissues are chronically exposed to hypoxia owing t

116 ith real-time PCR analysis of human prostate tumor tissue arrays that revealed the expression of 12-H

117 most dysfunctional subset of CD8+ T cells in tumor tissue as well as tumor-tissue Tregs with a highly

118 increased collagen deposition in metastatic tumor tissues as a direct consequence of amplified colla

119 (18)F-BMS-986192 bound to tumor tissues as a function of PD-L1 expression determin

120 anitumumab randomization, 331 had sufficient tumor tissue available and measurement of ligand express

121 tember 2014 who had preoperative CT data and tumor tissue available was studied.

122 Nanomedicine to overcome both systemic and tumor tissue barriers ideally should have a transformabl

123 lly visualized them within blood vessels and tumor tissues before, during and after magnetic field ex

124 significant difference in TUNEL staining in tumor tissue between mice treated with DOX and iRGD comp

125 urement of single longest diameter of viable tumor tissue (bias = 0 cm intraobserver versus bias = 0.

126 Archival tumor tissue blocks from 1,602 patients previously diagn

127 ransplantation of patient-derived pancreatic tumor tissue, BPTES nanoparticle monotherapy led to mode

128 umulation of nanoparticle-based therapies in tumor tissue but must be optimized to allow for intratum

129 osylated MUC1 on human cancer cell lines and tumor tissues but show no reactivity against fully-glyco

130 inflict localized and irreversible damage to tumor tissue by hyperthermia, without harming surroundin

131 Furthermore, targeting non-T cell-inflamed tumor tissues by antibody-guided LIGHT creates a T cell-

132 s selectively deregulated redox reactions in tumor tissues by increasing levels of reactive oxygen sp

133 epleted tumor-associated stroma in xenograft tumor tissues by inhibiting the SHH cellular signaling p

134 veral biological membranes and accumulate in tumor tissues by passing through abnormally leaky tumor

135 stimulating hormone (TSH) in both normal and tumor tissues can be assessed by using this approach.

136 The inadequate transport of drugs into the tumor tissue caused by its abnormal vasculature is a maj

137 ally dependent and coexpressed in normal and tumor tissues/cells.

138 13)C-pyruvate MRS imaging simultaneously for tumor tissue characterization and on a larger scale test

139 that were evaluated, CPT is detected in the tumor tissue collected 24-48 h after CRLX101 administrat

140 The tumor tissue collected for primary diagnosis was used in

141 oparticles" penetrate much deeper into brain tumor tissue compared to nanoparticles without a dense P

142 LIF was overexpressed in tumor tissue compared with healthy pancreas, but its rec

143 ich showed that low SIRT1 gene expression in tumor tissues compared with normal adjacent tissues pred

144 ated ( approximately 70 times) in colorectal tumor tissues compared with their normal pairs.

145 GFC, and VEGFR3 were increased in colorectal tumor tissues, compared with controls.

146 ging (DTI) with quantitative histopathologic tumor tissue composition in prostate cancer in a prelimi

147 Intravital microscopy of NP spread in breast tumor tissue confirmed a significant difference in tumor

148 complete loss of nuclear MSH3 in normal and tumor tissue, confirming the LoF effect and causal relev

149 llenging as most cancer sequencing uses bulk tumor tissue containing heterogeneous mixtures of cells.

150 between 4 antibodies revealed regression for tumor tissue cores (R2 = 0.42-0.91) and cell line cores

151 between 4 antibodies revealed regression for tumor tissue cores (R2 = 0.42-0.91) and cell line cores

152 ion, the accumulation in kidney, muscle, and tumor tissue correlated between FMT/CT and PET/MRI.

153 High levels of HGF protein in tumor tissues correlated with lower levels of receptor-i

154 Analysis of the diseased individuals' tumor tissue demonstrated high microsatellite instabilit

155 MMneu-flAP2C cell line was established from tumor tissue derived from MMTV-Neu/Tcfap2c(L/L) control

156 y correlated with Treg cells accumulation in tumor tissues derived from PDAC patients.

157 inoma subclassified by F nucleatum status in tumor tissue, determined by quantitative polymerase chai

158 In contrast, tumor tissues displayed an increase in phosphatidylinosi

159 Conclusion Mechanical tumor tissue disruption with pulsed focused ultrasound-i

160 The normal and tumor tissue distribution and the cell line reactivity o

161 ajor challenge for drug penetration in solid tumor tissues due to the complicated tumor microenvironm

162 B permeability and reflects the viability of tumor tissue during antiangiogenic therapy more reliably

163 s, thus facilitating the removal of residual tumor tissue during surgical procedures.

164 Complete removal of residual tumor tissue during surgical resection improves patient

165 greatly facilitated by the study of biopsied tumor tissue, especially at the time of drug resistance.

166 oxicity and inefficient penetration of brain tumor tissue even when it is placed directly in the brai

167 T silencing confirmed by Western blotting of tumor tissue ex vivo.

168 Comparison of simulated FNAs and matched tumor tissue exhibited a concordance frequency of 100% f

169 glycol) (PEG) density for penetration within tumor tissue extracellular matrix (ECM).

170 harge reversal from -7.4 to 8.2 mV at acidic tumor tissue, for enhanced tumor penetration and uptake

171 Expression studies in breast tumor tissues found SNP rs2787486 to be associated with

172 By immunohistochemical staining of hepatic tumor tissue from 155 patients, the expression of PTP1B

173 performed metabolomic profiling of serum and tumor tissue from 158 patients with high-grade serous ov

174 ologic effects of therapy, we analyzed blood/tumor tissue from 45 patients undergoing single or combi

175 In tumor tissue from breast cancer patients, beta3 was sign

176 d threshold that sufficiently differentiates tumor tissue from healthy tissue.

177 r (TFR1), the iron importer, is increased in tumor tissue from patients with high grade but not low g

178 inly regarding the differentiation of viable tumor tissue from treatment-related effects.

179 on upregulates Bcl2 in lung cancer cells and tumor tissues from clinical trial patients.

180 87 patients with neuroblastic tumors and in tumor tissues from the TH-MYCN NB mouse model.

181 In breast tumor tissues, GLI1 expression enhanced tissue identific

182 h as cancer or endothelial cells, as well as tumor/tissue grafts, can be encapsulated in the hydrogel

183 ed significant differences for benign versus tumor tissues, GS </= 3 + 3 versus GS >/= 3 + 4 tumors,

184 d in lung cancer cell lines and primary lung tumor tissues harboring a hypermethylated SOX30.

185 orthotopic xenografts models and human brain tumors, tissue heterogeneity in clinical brain tumors ha

186 IF methodology can be an invaluable tool for tumor tissue immune-profiling to allow multiple targets

187 a significant decrease in O-GlcNAcylation of tumor tissue in an ovarian tumor microarray.

188 ipheral zone (PZ), transition zone (TZ), and tumor tissue in both zones of the prostate by using a li

189 n rate should manifest fast diffusion in the tumor tissue in order to avoid generation of concentrati

190 le of targeted accumulation and retention in tumor tissue in response to overexpressed endogenous enz

191 use of this approach to visualize pancreatic tumor tissue in vivo as early as 1 h postinjection.

192 lyze the transcriptomes of healthy, NAT, and tumor tissues in 6506 samples across eight tissues and c

193 sly injected F. nucleatum localizes to mouse tumor tissues in a Fap2-dependent manner, suggesting tha

194 Here, we utilized alive tumor tissues in ex-vivo platform termed CANscript, whic

195 ealthy brain parenchyma and orthotopic brain tumor tissues in rats.

196 Their ability to be targeted to tumor tissues in vivo using the iRGD targeting peptide i

197 tially increased in PDACs, compared with non-tumor tissues, in tissue microarray analyses.

198 overexpression has been observed in several tumor tissues, including glioblastoma (GBM), and is cons

199 targeting on alphav integrins expressed near tumor tissue, iRGD encounters proteolytic cleavage to ex

200 ed significant accumulation of MAIT cells in tumor tissue, irrespective of tumor stage or localizatio

201 Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical si

202 We notice that tumor tissue is characterized by more intense drug extra

203 Molecular analysis of tumor tissue is improving patient stratification, allowi

204 an serve as a surrogate tumor biopsy when Rb tumor tissue is not available.

205 t deposition of CRLX101 nanoparticles in the tumor tissue is obtained.

206 t for hydrogen peroxide (H2O2) production in tumor tissue is strategically compiled into a H2O2-respo

207 trate that sufficient T cell infiltration in tumor tissues is a prerequisite for response to PD-L1 bl

208 a clear picture of their distribution within tumor tissues is lacking.

209 One of distinct features in tumor tissues is the elevated concentration of reactive

210 tions previously determined in corresponding tumor tissue led to further identification of six patien

211 reening the expression of these genes in the tumor tissue may suggest the best course of chemotherapy

212 In a pediatric embryonal brain tumor tissue microarray, we observed an association betw

213 was assessed by ERG immunohistochemistry on tumor tissue microarrays constructed from radical prosta

214 In human prostate tumor tissue microarrays, loss of PTEN correlates with i

215 xis were screened by immunohistochemistry in tumor tissue microarrays.

216 by the increased MRP1 expression within the tumor tissue microenvironment.

217 Within tumor tissue, mitochondria metabolism is frequently repr

218 We examined the role of Tet2 in tumor-tissue myeloid cells and found that Tet2 sustains

219 e DOX does not effectively upregulate DR5 in tumor tissues nor demonstrate synergy with TRAILPEG in H

220 nesis and is dramatically upregulated in the tumor tissue of individuals with GCT/PDB.

221 o the endothelium but may also include solid tumor tissue of nonprostatic cancers including melanoma

222 kappaB (NF-kappaB) signaling were boosted in tumor tissues of Apc Olfm4 double-mutant mice.

223 of IL1R2 were highly correlated with IL-6 in tumor tissues of CRC patients.

224 Tumor tissues of different origins have been shown to pr

225 Frozen and paraffin-embedded tumor tissues of different stages and isolated crypts we

226 nically relevant subgroups regardless of the tumors' tissue of origin, highlighting similarities in e

227 pressed differentially between tumor and non-tumor tissues, of which 1,504 were correlated with mRNA

228 ns in cfDNA identified the L858R mutation in tumor tissue or in cfDNA as a marker of shorter OS (haza

229 Extraction of 10 mg BRCA-/-, p53-/- breast tumor tissue or normal mammary gland tissue with methyl-

230 tissue confirmed a significant difference in tumor tissue penetration between the 62 and 110nm PEG-co

231 ch show significant loss of co-expression in tumor tissue, pointing to potential mitochondrial dysfun

232 CAR T-cells that are only effective locally (tumor tissue), potentially also increasing the choice of

233 However, the hypoxic environment in tumor tissue prevents the formation of oxygen free radic

234 n of immunosuppressive T-regulatory cells in tumor tissue promote immune tolerance.

235 Scoring macrophage infiltration in tumor tissue provides a prognostic assessment that is co

236 siRNA-L2 penetrated tumor tissue rapidly and homogeneously; 30 min after i.v

237 ro studies showed that secreted factors from tumor tissue reduced IFN-gamma production from MAIT cell

238 We hypothesized that the fraction of tumor tissue refractory to oxygen challenge (lack of pos

239 he sTRA glycan was significantly elevated in tumor tissue relative to adjacent pancreatic tissue in 3

240 10 samples showed a significant decrease in tumor tissues relative to matched pericarcinomatous tiss

241 reviously reported to be highly expressed in tumor tissues removed from patients with esophageal squa

242 Additionally, analysis of tumor tissue revealed a more complex pattern than observ

243 Analysis of human blood samples and tumor tissue revealed that a promoted VWF release combin

244 we compared the expression of DXME in breast tumor tissue samples from patients representing three et

245 In practice, solid tumor tissue samples obtained from clinical settings are

246 (mean [SD] age, 55.0 [10.8] years), 614 had tumor tissue samples scored for H&E sTILs and 427 for CD

247 is known that platelets can infiltrate into tumor tissue, secrete pro-angiogenic and pro-tumorigenic

248 valuate potential molecular targets in human tumor tissue sections.

249 unohistochemical analysis of clinical breast tumor tissues showed that high p62 expression levels wer

250 in seconds with single MS scans of necrotic tumor tissue smears, which further accelerates the ident

251 in situ hybridization 48 human normal and 24 tumor tissue specimens.

252 GenomePlex kit) in FFPE normal and tumor tissue specimens.

253 discloses high transcript levels in several tumor tissues, such as germ cell, breast, and ovarian tu

254 f DNA from formalin-fixed, paraffin-embedded tumor tissue, supporting clinical applications for this

255 However, tumor tissue tends to stiffen during solid tumor progres

256 bly improves oxygen transport to the hypoxic tumor tissues, thereby increasing the sensitivity of tum

257 her with reports describing BKV detection in tumor tissues, these results support an association betw

258 , 102 enrolled with 91 (89%) having adequate tumor tissue to complete sequencing.

259 8)F-FDG PET markers of glucose metabolism in tumor tissue to determine whether (18)F-FDG PET could be

260 high quality RNA could be obtained from FFPE tumor tissues to detect frozen tissue-derived prognostic

261 t of CD8+ T cells in tumor tissue as well as tumor-tissue Tregs with a highly active and suppressive

262 ons using simulations of clinically relevant tumor tissue types.

263 nical) and the kinetic parameter values of 3 tumor tissue types.

264 nical) and the kinetic parameter values of 3 tumor tissue types.

265 reliable indicator of ischemic changes that tumor tissues undergo, we subjected harvested xenograft

266 This study shows that direct priming of a tumor tissue using photosensitization rapidly activates

267 expression in an independent cohort of lung tumor tissues using quantitative RT-PCR.

268 ohistochemical labeling of DYRK1A in primary tumor tissues using tissue microarrays revealed strong t

269 us white matter of healthy volunteers and in tumor tissue versus normal-appearing white matter of pat

270 ivity of (18)F-FDG PET/CT to detect residual tumor tissue was 92% (95% confidence interval [CI], 75%-

271 Patients and Methods Tumor tissue was collected from 1,003 patients with node

272 The first patient's tumor tissue was investigated for secretin and VIP.

273 re devoid of vascular supply and >80% of the tumor tissue was necrotic.

274 ation of the label agent, 32.4 mug.g(-1), in tumor tissue was observed in the area of the injection o

275 erformed after the last imaging session, and tumor tissue was preserved for molecular analysis.

276 (18)F-FDG uptake of tumor tissue was quantified by maximum standardized upta

277 The tumor tissue was quantitatively assessed for TSPO expres

278 clonality with elevated PD-L1 IC staining in tumor tissue was strongly associated with poor clinical

279 found that high-expression of IL-6R mRNA in tumor tissues was a positive prognostic factor for overa

280 on, and direct measurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone p

281 mcitabine and its metabolites extracted from tumor tissue, we demonstrate reproducible chromatography

282 Using freshly resected tumor tissue, we describe an optimized ex vivo explant c

283 loped fluorescence quantification system for tumor tissues, we collected 3 types of GBM tissues on th

284 distribution of (64)Cu-ATSM and (64)CuCl2 in tumor tissue were compared with partial pressure of oxyg

285 ining chemotherapy regimen and had available tumor tissue were eligible to participate in this study.

286 Tumor tissues were analyzed by immunohistochemistry for

287 er levels of CD44v6 mRNA in human pancreatic tumor tissues were associated with increased expression

288 Tumor tissues were considered to have intact BMP signali

289 xpressed genes between breast cancer and non-tumor tissues were screened.

290 and its mRNA were predominantly found in the tumor tissue whereas VIP and its mRNA were scarce.

291 organoid generation protocols require fresh tumor tissue, which limits organoid research and clinica

292 TIPE1 expression compared with adjacent non-tumor tissues, which positively correlated with tumor pa

293 ng therapeutic reagents into cancer cells or tumor tissues while simultaneously generating unique sig

294 sound alone caused little adverse effects to tumor tissue, while the combined treatment triggered nec

295 nificantly reduces microvessel density in PC tumor tissues, while not inhibiting prostate cancer cell

296 d suppressor cells (MDSCs) were recruited to tumor tissue with a preferential accumulation of granulo

297 In addition, tumor tissue with higher RPS15A expression demonstrated

298 t model, the Gleason score and proportion of tumor tissue within each segment (segmental tumor burden

299 oprotective effects in the liver, but not in tumor tissue, without humoral adverse effects.

300 oprotective effects in the liver, but not in tumor tissue, without humoral adverse effects.