ライフサイエンスコーパス: ferroptosis

1 d peroxidation and oligodendrocyte loss (via ferroptosis).

2 normal cell function, signaling, and death (ferroptosis).

3 ells, ether-lipid synthesis protects against ferroptosis.

4 l factor for immune-initiated cell death via ferroptosis.

5 ell cycle arrest, senescence, apoptosis, and ferroptosis.

6 blastoma (GBM) involves neutrophil-triggered ferroptosis.

7 e stress and lipid peroxidation, and induced ferroptosis.

8 MX alter the lipid profile of cells to favor ferroptosis.

9 he non-caspase-dependent form of cell death, ferroptosis.

10 duction is governed by similar mechanisms as ferroptosis.

11 ew targets for the therapeutic modulation of ferroptosis.

12 n GBMs and reveals a pro-tumorigenic role of ferroptosis.

13 47 cells, as well as increase sensitivity to ferroptosis.

14 , resulting in resistance to necroptosis and ferroptosis.

15 ing that ALOX12 is critical for p53-mediated ferroptosis.

16 promotes tumour cell lipid peroxidation and ferroptosis.

17 80 fibrosarcoma cells, suggesting a role for ferroptosis.

18 l death, suggesting a link between AURKA and ferroptosis.

19 s resistance to cysteine-deprivation-induced ferroptosis.

20 rated fatty acids and to induce p53-mediated ferroptosis.

21 that additional factors govern resistance to ferroptosis.

22 that account for the resistance of cells to ferroptosis.

23 s, the unsubstituted lead exclusively caused ferroptosis.

24 ne to suppress phospholipid peroxidation and ferroptosis.

25 and without administration of inhibitors of ferroptosis.

26 ch was associated with reduced activation of ferroptosis.

27 AMPK inactivation sensitizes these cells to ferroptosis.

28 inhibition but dispensable for p53-mediated ferroptosis.

29 larization, lipid peroxide accumulation, and ferroptosis.

30 of monensin was not blocked by inhibitors of ferroptosis.

31 ion, all of which are important hallmarks of ferroptosis.

32 e in complement-deficient mice likely due to ferroptosis.

33 s may be much more sensitive to induction of ferroptosis.

34 th ferrostatin-1 (Fer-1) completely reverted ferroptosis.

35 t transport iron out of the cell, inhibiting ferroptosis.

36 harnessing reactive oxygen species to induce ferroptosis.

37 potential for anticancer therapy by inducing ferroptosis.

38 ependent, nonapoptotic cell death process of ferroptosis.

39 nction of a selenoperoxidase, GPX4, leads to ferroptosis.

40 yunsaturated fatty acids and is required for ferroptosis.

41 4 for survival and are highly susceptible to ferroptosis.

42 ulates reactive oxygen species (ROS)-induced ferroptosis.

43 urons and dynamic glutathione changes during ferroptosis.

44 ly, as previously unrecognized modulators of ferroptosis.

45 pid peroxidation (LPO) and cell death termed ferroptosis.

46 o the regulation of iron and mitochondria in ferroptosis.

47 er cell death by a mechanism consistent with ferroptosis.

48 bate LIP-induced oxidative stress to trigger ferroptosis.

49 eutic interventions in diseases that involve ferroptosis.

50 t both occur in late life to prime cells for ferroptosis.

51 deprived of extracellular matrix to undergo ferroptosis.

52 ve factor in the cell-death pathway known as ferroptosis.

53 show increased cancer risk due to defective ferroptosis.

54 r preventing degenerative diseases involving ferroptosis.

55 n that, in turn, results in the induction of ferroptosis.

56 RF2 in protecting matrix-deprived cells from ferroptosis.

57 duces ER stress and sensitises CRPC cells to ferroptosis.

58 ll death through a mechanism consistent with ferroptosis.

59 ainst lipid peroxidation and thereby promote ferroptosis.

60 coenzyme A, which, together, down-regulated ferroptosis.

61 glutathione (such as cysteine), can trigger ferroptosis(3).

62 rlie the sensitivity of a given cell type to ferroptosis(7) is crucial to understand the pathophysiol

63 metastatic property are highly sensitive to ferroptosis(8).

64 various treatments-are highly susceptible to ferroptosis(8,9).

65 biomarkers are all closely associated with 'ferroptosis', a recently discovered form of programmed c

66 Ferroptosis, a cell death process driven by cellular met

67 Increases in lipid peroxidation can cause ferroptosis, a form of cell death triggered by inhibitio

68 Ferroptosis, a form of iron-dependent, nonapoptotic cell

69 eath are tightly linked in the phenomenon of ferroptosis, a form of regulated cell death driven by pe

70 expected inhibitory role of energy stress on ferroptosis, a form of regulated cell death induced by i

71 bition of glutathione biosynthesis, triggers ferroptosis, a non-apoptotic form of cell death.

72 Ferroptosis, a non-apoptotic form of programmed cell dea

73 ogenic signaling as well as the discovery of ferroptosis, a novel iron-dependent form of cell death.

74 Ferroptosis, a novel mode of cell death elicited by iron

75 Activation of ferroptosis, a recently described mechanism of regulated

76 mpanied by expression of several markers for ferroptosis, a relatively newly described form of iron-m

77 ion of lymph may protect melanoma cells from ferroptosis-a form of iron-dependent cell death, thereby

78 iple cell death pathways, possibly including ferroptosis-a recently described cell death pathway that

79 Erastin, the ferroptosis activator, binds to voltage-dependent anion

80 g avenues to overcome the drug resistance of ferroptosis activators.

81 ncer cells were more sensitive and underwent ferroptosis after treatment with GPX4 inhibitors.

82 otective form of regulated cell death termed ferroptosis, all depend on iron metabolism.

83 Lipid peroxidation is a salient feature of ferroptosis, an iron-dependent nonapoptotic cell death.

84 pression, accumulating evidence reveals that ferroptosis, an iron-dependent, nonapoptotic form of cel

85 iated cholesterol uptake are also subject to ferroptosis, an oxygen- and iron-dependent cell death me

86 Ferroptosis-an iron-dependent, non-apoptotic cell death

87 Inhibition of ferroptosis and ACSL4 mitigated the ferroptotic damage i

88 Pretreatment with Lip-1 inhibited ferroptosis and ameliorated lung IR-induced injury in an

89 high basal AMPK activation are resistant to ferroptosis and AMPK inactivation sensitizes these cells

90 K and reveals an unexpected coupling between ferroptosis and AMPK-mediated energy-stress signalling.

91 Inhibition of SCD1 induced both ferroptosis and apoptosis.

92 The concomitant activation of ferroptosis and autophagy by 15LO1-PEBP1 complexes and t

93 Although ferroptosis and cellular metabolism interplay with one a

94 y mechanisms linking cholesterol uptake with ferroptosis and determine the potential role of the high

95 ells from lymph nodes were more resistant to ferroptosis and formed more metastases after intravenous

96 to understand the pathophysiological role of ferroptosis and how it may be exploited for the treatmen

97 ined data support a positive role for p53 in ferroptosis and identify CoA as a regulator of this cell

98 mitochondria in cysteine-deprivation-induced ferroptosis and implicates ferroptosis in tumor suppress

99 study identifies OTUB1 as a key regulator of ferroptosis and implicates it as a potential target in c

100 nvironment thus protects melanoma cells from ferroptosis and increases their ability to survive durin

101 tivated using chemical compounds to suppress ferroptosis and inflammation.

102 -) subunit, Slc7a11, induced tumor-selective ferroptosis and inhibited PDAC growth.

103 Pharmacologic inducers of ferroptosis and mechanical stretch injury resulted in ce

104 We explored the relative contributions of ferroptosis and necroptosis to folic acid (FA)-induced A

105 tuent shifted the mode of action toward both ferroptosis and necroptosis, while the analogously chlor

106 regulated cell death, including necroptosis, ferroptosis and pyroptosis.

107 c acid (DGLA; 20:3n-6) can trigger germ-cell ferroptosis and sterility in the nematode Caenorhabditis

108 spontaneous preterm birth is associated with ferroptosis and that inhibition of GPX4 causes ferroptot

109 Given the importance of lipid metabolism in ferroptosis and the key role of lipids in ovarian cancer

110 reported inhibitor of P4HB, directly induced ferroptosis and was highly synergistic with erastin.

111 on contributes to iron-dependent cell death (ferroptosis) and other disease pathologies including can

112 thione/GPX4-independent axes for suppressing ferroptosis, and insight into the regulation of iron and

113 eroxidase 4 (GPX4) is a central regulator of ferroptosis, and protects cells by neutralizing lipid pe

114 role for PLA2G6 in attenuating trophoblastic ferroptosis, and provided mechanistic insights into the

115 eoxPLs have roles in cellular events such as ferroptosis, apoptosis, and blood clotting and diseases

116 s of human GBMs support that neutrophils and ferroptosis are associated with necrosis and predict poo

117 Together, these findings implicate ferroptosis as a major mechanism of necrosis in Mtb infe

118 endent, GPX4 mediated cell death, suggesting ferroptosis as a major mechanism.

119 Thus, our study identifies ferroptosis as the underlying nature of necrosis in GBMs

120 gents that induce iron-dependent cell death (ferroptosis) as well as iron chelators, and thus creates

121 re we identify an intrinsic vulnerability to ferroptosis associated with the unique metabolic state i

122 energy stress on ferroptosis in vitro and on ferroptosis-associated renal ischaemia-reperfusion injur

123 This strategy provides a perspective on ferroptosis-based immunotherapy.

124 lacking alpha6beta4 is sufficient to trigger ferroptosis because GPX4 is suppressed.

125 uire an inducer, such as erastin, to undergo ferroptosis because they sustain GPX4 expression, despit

126 therto unappreciated regulatory mechanism of ferroptosis but also identifies potential therapeutic ta

127 crucial role in cysteine-deprivation-induced ferroptosis but not in that induced by inhibiting glutat

128 interactions mediated by E-cadherin suppress ferroptosis by activating the intracellular NF2 (also kn

129 ase glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid hydroperoxides into non-

130 del to study the induction and modulation of ferroptosis by dietary fats and indicate that endogenous

131 GPX4) uses glutathione to protect cells from ferroptosis by eliminating phospholipid peroxides.

132 further demonstrate that the suppression of ferroptosis by FSP1 is mediated by ubiquinone (also know

133 iling we show that peroxisomes contribute to ferroptosis by synthesizing polyunsaturated ether phosph

134 degenerative conditions(2), and induction of ferroptosis by the inhibition of GPX4 has emerged as a t

135 transcriptional co-activator YAP to promote ferroptosis by upregulating several ferroptosis modulato

136 Here we show that ferroptosis can be regulated non-cell-autonomously by ca

137 Ferroptosis can be triggered by depleting the cell of th

138 Ferroptosis can be triggered through either the extrinsi

139 cinoma cells that are initially sensitive to ferroptosis can switch to a ferroptosis-resistant state

140 This study aimed to investigate whether ferroptosis contributed to the pathogenesis of in vitro

141 xidation in tumour cells, and that increased ferroptosis contributes to the anti-tumour efficacy of i

142 Ferroptosis contributes to the antitumour function of se

143 ent glutathione peroxidase 4 (GPX4) inhibits ferroptosis, converting unstable ferroptotic lipid hydro

144 rrostatin-1 (Fer-1), a specific inhibitor of ferroptosis, decreases the level of pro-ferroptotic hydr

145 We demonstrate that blocking ferroptosis, either by inhibition of lipid peroxidation

146 optotic gene(11), confers protection against ferroptosis elicited by GPX4 deletion.

147 at this supplementation prevents spontaneous ferroptosis, especially when it contains polyunsaturated

148 Here we investigate the mechanism of ferroptosis execution and discover that ferroptotic cell

149 With respect to the immunogenicity of ferroptosis, Fer-1 prevented the upregulation of IL-33,

150 Ferroptosis has been implicated in the pathological cell

151 To date, ferroptosis has been thought to be controlled only by th

152 This causal link between alpha6beta4 and ferroptosis has implications for cancer biology and ther

153 Ferroptosis has previously been implicated in the cell d

154 Ferroptosis has recently been implicated in multiple dis

155 Previous studies have suggested that ferroptosis has the ability to spread through cell popul

156 le, a regulated mechanism of necrosis called ferroptosis has the unusual ability to spread between ce

157 n driving susceptibility to and evasion from ferroptosis, highlights PUFA-ePL as a distinct functiona

158 Cells differ in their sensitivity to ferroptosis, however, and a key challenge is to understa

159 y synergizes with GPX4 inhibitors to trigger ferroptosis in a number of cancer entities.

160 expression of GPX4 and higher sensitivity to ferroptosis in ACCs.

161 Oleic acid protected melanoma cells from ferroptosis in an Acsl3-dependent manner and increased t

162 11), rendered cancer cells more sensitive to ferroptosis in an orthotopic mouse model of malignant me

163 ss in Arabidopsis thaliana The similarity of ferroptosis in animal cells and ferroptosis-like death i

164 CD44 expression suppressed ferroptosis in cancer cells in an OTUB1-dependent manner

165 an Nrf2-operated pathological program toward ferroptosis in cardiomyocytes, thereby worsening the pro

166 rdinated iron metabolism, thereby leading to ferroptosis in cardiomyocytes.

167 We found that MDM2 and MDMX facilitate ferroptosis in cells with or without p53.

168 istration of CoA provides protection against ferroptosis in cultured mouse and human cells, as well a

169 of SLC7A11 and the CD44-mediated effects on ferroptosis in human cancers.

170 Exogenous DGLA is also sufficient to induce ferroptosis in human cells, pinpointing this omega-6 PUF

171 omplexes generate lipid-based ROS and induce ferroptosis in leukemia and neuroblastoma cell lines.

172 lines, and that FSP1 mediates resistance to ferroptosis in lung cancer cells in culture and in mouse

173 contribute to decreased oxidative stress and ferroptosis in lymph, including higher levels of glutath

174 e discuss the core process and regulation of ferroptosis in mammalian cells, as well as its therapeut

175 demonstrating a translatable means to induce ferroptosis in PDAC.

176 placental dysfunction, the possible role of ferroptosis in placental dysfunction is largely unknown.

177 n tension and protects cells from undergoing ferroptosis in response to oxidative damage.

178 Notably, a similar mechanism also modulates ferroptosis in some non-epithelial cells.

179 We show that FIPC-1 induces ferroptosis in susceptible cell types and labels cellula

180 privation-induced ferroptosis and implicates ferroptosis in tumor suppression.

181 ll-mediated anti-tumour immunity and induced ferroptosis in tumour cells.

182 cal inhibition of SCD1 induces apoptosis and ferroptosis in vitro and in vivo Combination therapies o

183 s the protective effects of energy stress on ferroptosis in vitro and on ferroptosis-associated renal

184 inhibition of cysteine transport to trigger ferroptosis in vitro and slow tumour growth.

185 igodendrocytes demonstrated key hallmarks of ferroptosis including lipid peroxidation, abnormal iron

186 B1 neuroblastoma cells was solely induced by ferroptosis, independent of the used substituents.

187 Notably, ALOX12 is dispensable for ferroptosis induced by erastin or GPX4 inhibitors; conve

188 adherent epithelial and carcinoma cells from ferroptosis induced by erastin.

189 so-PE and oxidized fatty acid, in mitigating ferroptosis induced by GPX4 inhibition in vitro or by hy

190 ALOX12 inactivation diminishes p53-mediated ferroptosis induced by reactive oxygen species stress an

191 ficantly potentiated the antitumor effect of ferroptosis inducers in both ovarian cancer cell lines a

192 combined treatment with SCD1 inhibitors and ferroptosis inducers may provide a new therapeutic strat

193 The combination of SCD1 inhibitors and ferroptosis inducers may provide a new therapeutic strat

194 Combination therapies of SCD1 inhibitors and ferroptosis inducers significantly decrease ovarian tumo

195 uction of lipid peroxides and is a target of ferroptosis inducers, such as erastin.

196 but also iron salophene complexes are potent ferroptosis inducers, which can be optimized as antitumo

197 these target genes sensitized cells to known ferroptosis inducers, while PACMA31, a previously report

198 n may predict sensitivity of some cancers to ferroptosis inducers.

199 Here we introduce Ferroptosis Inducing Peroxide for Chemoproteomics-1 (FIP

200 f death occurs following treatment with some ferroptosis-inducing agents, including erastin(2,9) and

201 ective strategy to sensitize cancer cells to ferroptosis-inducing chemotherapeutic agents.

202 Propagation of a ferroptosis-inducing signal occurs upstream of cell rupt

203 the responsiveness of cancer cells to future ferroptosis-inducing therapies.

204 Ferroptosis induction is a promising approach in treatin

205 es(8), but not upon direct inhibition of the ferroptosis-inhibiting enzyme glutathione peroxidase 4 (

206 mbrane repair, inflammation suppression, and ferroptosis inhibition.

207 sized through lymph, became dependent on the ferroptosis inhibitor GPX4.

208 tly, the administration of liproxstatin-1 (a ferroptosis inhibitor), clophosome-mediated macrophage d

209 ferrostatin-1 (Fer-1), a well-characterized ferroptosis inhibitor, as well as by iron chelation.

210 Ferroptosis inhibitors blocked death from NRF2 downregul

211 Cells that were pretreated with chemical ferroptosis inhibitors formed more metastases than untre

212 Why certain stimuli trigger ferroptosis instead of another form of cell death, and w

213 mechanism that enables alpha6beta4 to evade ferroptosis involves its ability to protect changes in m

214 In ferroptosis, iron-mediated free radicals trigger lipid p

215 Ferroptosis is a form of cell death that differs from ap

216 Ferroptosis is a form of cell death that results from th

217 Ferroptosis is a form of programmed cell death that is p

218 Ferroptosis is a form of regulated cell death characteri

219 Ferroptosis is a form of regulated cell death that is ca

220 Ferroptosis is a more recently recognized form of cell d

221 Ferroptosis is a newly defined form of regulated cell de

222 Ferroptosis is a regulated form of cell death that occur

223 Ferroptosis is a regulated form of necrotic cell death t

224 Ferroptosis is a regulated necrosis process driven by ir

225 Ferroptosis is a type of regulated necrosis induced by a

226 Thus, T cell-promoted tumour ferroptosis is an anti-tumour mechanism, and targeting t

227 Ferroptosis is an iron-dependent form of cell death resu

228 Ferroptosis is an iron-dependent form of necrotic cell d

229 Ferroptosis is an iron-dependent form of nonapoptotic ce

230 Ferroptosis is an iron-dependent, oxidative form of non-

231 Ferroptosis is an iron-dependent, oxidative, nonapoptoti

232 Ferroptosis is defined as an iron-dependent form of regu

233 However, precisely how susceptibility to ferroptosis is dynamically regulated remains poorly unde

234 oral scaling of lifespan is not evident when ferroptosis is inhibited, consistent with this cell deat

235 It is unclear whether, and how, ferroptosis is involved in T cell immunity and cancer im

236 It is well established that ferroptosis is primarily controlled by glutathione perox

237 These data suggest that ferroptosis is the primary cause of FA-AKI and that immu

238 ated by active mechanisms of execution(3-6), ferroptosis is thought to result from the accumulation o

239 Ferroptosis is triggered by lipid peroxidation and is ti

240 nother, whether mitochondria are involved in ferroptosis is under debate.

241 ing of regulated necrosis as they identify a ferroptosis-like cell death in Arabidopsis thaliana.

242 vascular development, was found to involve a ferroptosis-like cell death process.

243 rly polarized magnetic field (MF) to enhance ferroptosis-like cell-death mediated immune response, as

244 sion is achieved by Fenton reaction-mediated ferroptosis-like cell-death.

245 imilarity of ferroptosis in animal cells and ferroptosis-like death in plants suggests that oxidative

246 Ferroptosis likely serves a tumor suppressing function i

247 ath (apoptosis, necroptosis, pyroptosis, and ferroptosis) mainly in mammals, this Perspective explore

248 FA-AKI and that immunogenicity secondary to ferroptosis may further worsen the damage, although necr

249 e, post-developmental interventions to limit ferroptosis may promote healthy aging.

250 irst time, that CZ induces demyelination via ferroptosis-mediated rapid loss of oligodendrocytes.

251 vitro(7,8), there is emerging evidence that ferroptosis might be implicated in a variety of patholog

252 promote ferroptosis by upregulating several ferroptosis modulators, including ACSL4 and TFRC.

253 he lipid peroxidase GPX4 for protection from ferroptosis of inner, matrix-deprived cells.

254 rian cancer, we examined the contribution to ferroptosis of stearoyl-CoA desaturase (SCD1, SCD), an e

255 The extent of ferroptosis on the mode of action is regulated by simple

256 were subjected to pharmacologic induction of ferroptosis or mechanical stretch injury with and withou

257 ging of cardiac transplants, we uncover that ferroptosis orchestrates neutrophil recruitment to injur

258 udy demonstrates that energy stress inhibits ferroptosis partly through AMPK and reveals an unexpecte

259 ses revealed that several key players of the ferroptosis pathway are hypermethylated and/or mutated i

260 tifies an ALOX12-mediated, ACSL4-independent ferroptosis pathway that is critical for p53-dependent t

261 (GPX4), the most downstream component of the ferroptosis pathway.

262 Importantly, the disparate ferroptosis phenotypes related to the P47S polymorphism

263 that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, preserved renal function and decreased hist

264 n cancers, and functions to "dub" (trim) the ferroptosis process in cancer cells and promotes tumor d

265 l screen increased GPX4 activity, suppressed ferroptosis, reduced pro-inflammatory lipid mediator pro

266 Ferroptosis, regulated cell death characterized by the i

267 We sought a common ferroptosis regulator for 15LO.

268 discovery opportunities for inflammation and ferroptosis-related diseases.

269 This SnapShot provides an overview of ferroptosis-related pathways, including relevant biomole

270 nt, malondialdehyde, and glutathione levels, ferroptosis-related protein expression, and mitochondria

271 Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused b

272 t FSP1 expression positively correlates with ferroptosis resistance across hundreds of cancer cell li

273 These findings reveal that ferroptosis resistance can be driven by a prominin2-MVB-

274 Prominin2 facilitates ferroptosis resistance in mammary epithelial and breast

275 RNA-seq to identify genes that contribute to ferroptosis resistance, we discovered that pro-ferroptot

276 factor mitochondrial 2 (AIFM2)) as a potent ferroptosis-resistance factor.

277 lly sensitive to ferroptosis can switch to a ferroptosis-resistant state in vivo in mice, which is as

278 hanolamine (PE) participate in apoptosis and ferroptosis, respectively.

279 hemia reperfusion injury where inhibition of ferroptosis resulted in reduced infarct size, improved l

280 lles peroxisomes as critical contributors to ferroptosis sensitivity in human renal and ovarian carci

281 phospholipid composition(9,10) contribute to ferroptosis sensitivity, no cell-autonomous mechanisms h

282 Together, we identified ferroptosis signaling in the human and mouse placenta, e

283 The roles of ferroptosis-specific inhibitor, liproxastin-1 (Lip-1), a

284 munotherapy-activated CD8(+) T cells enhance ferroptosis-specific lipid peroxidation in tumour cells,

285 ty is essential for MDM2 and MDMX to promote ferroptosis, suggesting that the MDM2-MDMX complex regul

286 These findings define a ferroptosis suppression pathway and indicate that pharma

287 hetic lethal CRISPR-Cas9 screen, we identify ferroptosis suppressor protein 1 (FSP1) (previously know

288 AIFM2, which we renamed ferroptosis suppressor protein 1 (FSP1) and which was in

289 antioxidant enzyme reported as an important ferroptosis suppressor, in the pancreas of mice with cer

290 The ferroptosis-susceptible cell state can either pre-exist

291 superoxide source were better protected from ferroptosis than those treated with phenoxazine (or its

292 ition; GPX4 inhibition is a known trigger of ferroptosis that by itself minimally affects AML cells.

293 onfirmed using a small-molecule inhibitor of ferroptosis that prevents CZ-induced loss of OL and demy

294 mic analyses further link AMPK regulation of ferroptosis to AMPK-mediated phosphorylation of acetyl-C

295 nhibitors; conversely, ACSL4 is required for ferroptosis upon GPX4 inhibition but dispensable for p53

296 ell cycle arrest, senescence, apoptosis, and ferroptosis, were tumor prone but failed to develop earl

297 (ECM) detachment is a physiologic trigger of ferroptosis, which is evaded by alpha6beta4.

298 tioxidant whose depletion has been linked to ferroptosis, while concomitantly decreasing unsaturated

299 line is remarkably sensitive to induction of ferroptosis, while mitotane does not induce this iron-de

300 remarkable decrease in GPX4, an inhibitor of ferroptosis, with an increase in cleaved PARP and caspas