interacts_with DB01278?
Eupolyphaga sinensis walker displays inhibition on hepatocellular carcinoma through regulating cell growth and metastasis signaling . Tumor growth and metastasis are responsible for most cancer patients ' deaths . Here , we report that eupolyphaga sinensis walker has an essential role in resisting hepatocellular carcinoma growth and metastasis . Compared with proliferation , colony formation , transwell assay and transplantable tumor in nude mouse in vitro and vivo , eupolyphaga sinensis walker extract ( ESWE ) showed good inhibition on the SMMC-7721 cell growth and metastasis . Using genome-wide microarray analysis , we found the down-regulated growth and metastasis factors , and selected down-regulated genes were confirmed by real-time PCR . Knockdown of a checkpoint PKCβ by siRNA significantly attenuated tumor inhibition and metastasis effects of ESWE . Moreover , our results indicate ESWE inhibits HCC growth by not only downregulating the signaling of PKCβ , Akt , m-TOR , Erk1/2 , MEK-2 , Raf and JNK-1 , but also increasing cyclin D1 protein levels and decreasing amount of cyclin E , cyclin B1 and cdc2 of the cycle proteins . At the same time , ESWE reduced P08253 , P14780 and P61073 , P00747 , NFκB and P04637 activities . Overall , our studies demonstrate that ESWE is a key factor in growth and metastasis signaling inhibitor targeting the PKC , AKT , MAPK signaling and related metastasis signaling , having potential in cancer therapy . The effectiveness of lurasidone as an adjunct to lithium or divalproex in the treatment of bipolar disorder . The majority of patients with bipolar disorder spend a lot of time in depressive episodes that impose a great burden on patients , caregivers , and society and accounts for the largest part of the morbidity-mortality of the illness . DB08815 is an atypical antipsychotic with a potent binding affinity as antagonist for D2 , 5- Q13049 , P34969 , and partial agonist at P08908 receptors . Affinity for other receptors as H1 and muscarinic were negligible . DB08815 was approved in 2010 for the treatment of schizophrenia and recently , 2013 , for bipolar depression in monotherapy and an adjunct to lithium or valproate . Clinical trials have established that lurasidone adjuvant to lithium or valproate has more efficacy than the placebo and is associated with minimal weight gain and no clinically meaningful alterations in glucose , lipids , or the QT interval . Additional studies are desirable to know the clinical profile of lurasidone in long-term treatment , in patients with bipolar II disorders , and versus other antipsychotic agents . Desmopressin ( DB00035 ) induces NO production in human endothelial cells via V2 receptor- and DB02527 -mediated signaling . The hemostatic agent desmopressin ( DB00035 ) also has strong vasodilatory effects . DB00035 is a selective agonist for the vasopressin V2 receptor ( P30518 ) , which is coupled to DB02527 -dependent signaling . DB00035 -induced vasodilation may be due to endothelial NO synthase ( P29474 ) activation . This hypothesis implies DB02527 -mediated P29474 activation . It also implies wide extrarenal , endothelial P30518 expression . We show that in human umbilical vein endothelial cells ( HUVECs ) the DB02527 -raising agents forskolin and epinephrine increase NO production , as measured by a l-NMMA-inhibitable rise in cellular cGMP content . They also increase P29474 enzymatic activity , in a partly calcium-independent manner . DB02527 -mediated P29474 activation is associated with phosphorylation of residue Ser1177 , in a phosphatidyl inositol 3-kinase ( PI3K ) -independent manner . HUVECs do not express P30518 . However , after heterologous P30518 expression , DB00035 induces DB02527 -dependent P29474 activation via Ser1177 phosphorylation . We have previously found P30518 expression in cultured lung endothelial cells . By real time quantitative RT-PCR , we now find a wide P30518 distribution notably in heart , lung and skeletal muscle . These results indicate that DB00035 and other DB02527 -raising agents can activate P29474 via PI3K-independent Ser1177 phosphorylation in human endothelial cells . This mechanism most likely accounts for DB00035 -induced vasodilation . P10275 -induced tumor suppressor , B2CW77 , inhibits breast cancer growth and transcriptionally activates p53/p73-mediated apoptosis in breast carcinomas . P10275 ( AR ) expression by immunohistochemistry correlates with better prognosis and survival among breast cancer patients . We and others have shown that AR inhibits proliferation and induces apoptosis in breast cancer cells . However , the mechanism of AR 's anti-tumor effect in breast cancer is still not fully understood . Our recent study indicates that AR upregulates expression of tumor suppressor gene P60484 by promoter activation in breast cancer . B2CW77 , encoding B2CW77 protein , is a newly identified gene , which shares a bidirectional promoter with P60484 and is transcribed in the opposite direction . So far , the function of B2CW77 has never been studied in tumorigenesis . Here , we define B2CW77 as a tumor suppressor in breast carcinomas , which inhibits tumor growth and invasiveness . After analyzing 188 normal breast and 1247 malignant breast cancer tissues , we observed the loss of B2CW77 in multiple breast cancer subtypes and this decreased B2CW77 expression associates with tumor progression and increasing histological grade in invasive carcinomas . We characterize B2CW77 , for the first time , as a transcription factor , directly promoting the expression of P04637 and O15350 , with consequent elevated apoptosis and cell cycle arrest in breast cancer cells . We demonstrate , in vitro and in murine xenograph models , that both B2CW77 and P60484 are AR-target genes , mediating androgen-induced growth inhibition and apoptosis in breast cancer cells . Our observations suggest that B2CW77 might be used as a potential prognostic marker and novel therapy target for breast carcinomas . The sulphydryl containing P12821 inhibitor Zofenoprilat protects coronary endothelium from Doxorubicin-induced apoptosis . Pediatric and adult cancer patients , following the use of the antitumor drug Doxorubicin develop cardiotoxicity . Pharmacological protection of microvascular endothelium might produce a double benefit : ( i ) reduction of myocardial toxicity ( the primary target of Doxorubicin action ) and ( ii ) maintenance of the vascular functionality for the adequate delivery of chemotherapeutics to tumor cells . This study was aimed to evaluate the mechanisms responsible of the protective effects of the angiotensin converting enzyme inhibitor ( ACEI ) Zofenoprilat against the toxic effects exerted by Doxorubicin on coronary microvascular endothelium . We found that exposure of endothelial cells to Doxorubicin ( 0.1-1μM range ) impaired cell survival by promoting their apoptosis . P27361 /2 related p53 activation , but not reactive oxygen species , was responsible for Doxorubicin induced caspase-3 cleavage . P04637 mediated-apoptosis and impairment of survival were reverted by treatment with Zofenoprilat . The previously described PI-3K/ P29474 /endogenous fibroblast growth factor signaling was not involved in the protective effect , which , instead , could be ascribed to cystathionine gamma lyase dependent availability of H2S from Zofenoprilat . Furthermore , considering the tumor environment , the treatment of endothelial/tumor co-cultures with Zofenoprilat did not affect the antitumor efficacy of Doxorubicin . In conclusion the ACEI Zofenoprilat exerts a protective effect on Doxorubicin induced endothelial damage , without affecting its antitumor efficacy . Thus , sulfhydryl containing ACEI may be a useful therapy for Doxorubicin-induced cardiotoxicity . P10997 -induced suppression of P01160 secretion through receptors for CGRP1 and salmon calcitonin . P10997 cosecretes with insulin from pancreatic beta-cells and shows high sequence homology with P80511 , adrenomedullin , and salmon calcitonin . This study aimed to investigate the effect of amylin on the atrial hemodynamics and P01160 release from rat atria and to identify its receptor subtypes . Isolated perfused left atria from either control or streptozotocin-treated rats were paced at 1.3 Hz . The concentration of P01160 was measured by radioimmunoassay and the translocation of ECF was measured by [ 3H ] -inulin clearance . Rat amylin increased atrial contractility and suppressed the release of P01160 . Rat P80511 showed similar effects but was approximately 300-fold more potent than amylin . Pretreatment with receptor antagonist for CGRP1 [ rat alpha- P80511 ( 8-37 ) ] or salmon calcitonin [ acetyl- ( Asn30 , Tyr32 ) -calcitonin(8-32) , ( AC 187 ) ] blocked the suppressive effect of P01160 release and the positive inotropic effect by rat amylin . However , receptor antagonists for amylin [ amylin ( 8-37 ) , acetyl-amylin ] did not block those effects . P10997 ( 8-37 ) , acetyl-amylin , or rat alpha- P80511 ( 8-37 ) alone accentuated the release of P01160 with no changes in atrial contractility . The effect of rat amylin and rat amylin ( 8-37 ) on the P01160 release was attenuated in streptozotocin-treated rats . We suggest that amylin suppressed P01160 release with increased atrial contractility through receptors for CGRP1 and salmon calcitonin and the attenuation of amylin and its antagonist on P01160 release from streptozotocin-treated rat atria may be due to the downregulation of amylin receptor . Determination of fenofibric acid concentrations by HPLC after anion exchange solid-phase extraction from human serum . Triglycerides are increasingly being recognized as a risk factor for cardiovascular disease . Research efforts to identify sources of variability in triglyceride-lowering response to the lipid-lowering drug fenofibrate require quantification of the active acidic form of this Q07869 agonist . Anion-exchange solid-phase extraction , in combination with reverse-phase high-performance liquid chromatography ( HPLC ) , rapidly and accurately determines steady-state fenofibric acid serum concentrations . Chromatographic separation under isocratic conditions , with use of ultraviolet detection at 285 nm , provides clean baseline and sharp peaks for clofibric acid , 1-napthyl acetic acid ( internal standards ) , and fenofibric acid . Commonly prescribed and over-the-counter nonsteroidal anti-inflammatory drugs ( NSAIDs ) were screened for assay interference , and the assay was employed to quantify fenofibric acid in more than 800 human subject specimens . DB01039 analysis was found to be linear over the range of 0.5 to 40 mg/L and was validated with either internal standard . Accuracies ranged from 98.65 % to 102.4 % , whereas the within- and between-day precisions ranged from 1.0 % to 2.2 % and 2.0 % to 6.2 % , respectively . NSAIDs had minimal interference with the assay , which succeeded in quantifying fenofibric acid in more than 843 of 846 serum samples from human subjects , many taking a variety of coadministered medications . Anion-exchange solid-phase extraction in combination with reverse-phase HPLC accurately determines steady-state fenofibric acid serum concentrations in humans without interference from NSAIDs or commonly administered medications . This method is suitable for quantification of fenofibric acid for clinical pharmacokinetic studies in patients with dyslipidemia . The role of peroxisome proliferator-activated receptor γ in pancreatic β cell function and survival : therapeutic implications for the treatment of type 2 diabetes mellitus . The pathogenesis of type 2 diabetes mellitus involves both peripheral insulin resistance and dysfunctional insulin secretion from the pancreatic β cell . Currently , there is intense research focus on delineating the etiologies of pancreatic β cell dysfunction in type 2 diabetes . However , there remains an unmet clinical need to establish therapeutic guidelines and strategies that emphasize the preservation of pancreatic β cell function in at-risk and affected individuals . Thiazolidinediones are orally active agents approved for use in type 2 diabetes and act as agonists of the nuclear hormone receptor Q07869 -γ . These drugs improve insulin sensitivity , but there is also a growing appreciation of Q07869 -γ actions within the β cell . Q07869 -γ has been shown to regulate directly key β cell genes involved in glucose sensing , insulin secretion and insulin gene transcription . Further , pharmacologic Q07869 -γ activation has been shown to protect against glucose- , lipid- , cytokine- and islet amyloid polypeptide ( P10997 ) -induced activation of numerous stress pathways . This article will review the mechanisms by which Q07869 -γ activation acts to maintain β cell function and survival in type 2 diabetes mellitus and highlight some of the current controversies in this field . A combination of molecular cytogenetic analyses reveals complex genetic alterations in conventional renal cell carcinoma . Here we report the complex pattern of genomic imbalances and rearrangements in a panel of 19 renal cell carcinoma cell lines detected with molecular cytogenetic analysis . Consistent heterogeneity in chromosome number was found , and most cell lines showed a near-triploid chromosome complement . Several cell lines showed deletions of the P04637 ( alias p53 ) , CDKN2A ( alias p16 ) , and P40337 genes . Multiplex fluorescence in situ hybridization ( M- Q5TCZ1 ) analysis revealed chromosome 3 translocated to several other partners chromosomes , as well as breakage events commonly affecting chromosomes 1 , 5 , 8 , 10 , and 17 . The most common abnormality detected with comparative genomic hybridization ( CGH ) was deletions of chromosome 3p , with loss of the Q9NS23 , P49789 , and p44S10 loci frequently involved . CGH gain of 5q showed overrepresentation of the P18146 and P07333 genes . Recurrent alterations to chromosome 7 included rearrangement of 7q11 and gains of the P00533 , O15164 , and P35250 genes . Several lines exhibited rearrangement of 12q11 approximately q14 and overrepresentation of P11802 and SAS loci . M- Q5TCZ1 revealed several other recurrent translocations , and CGH findings included loss of 9p , 14q , and 18q and gain of 8q , 12 , and 20 . Further genomic microarray changes included loss of Q13126 , IGH@ , P28222 , and Q13485 ( previously Q13485 ) and gains of MYC and P11387 . An excellent correlation was observed between the genomic array and Q5TCZ1 data , demonstrating that this technique is effective and accurate . The aberrations detected here may reflect important pathways in renal cancer pathogenesis . DB00819 inhibits stimulated feline liver and gallbladder bicarbonate secretion . Bile acidification is a key factor in preventing calcium carbonate precipitation and gallstone formation . P00918 ( CA II ) , that is inhibited by acetazolamide , plays a role in regulation of the acid-base balance in many tissues . This study examines the effect of acetazolamide on secretin- and vasoactive intestinal peptide ( P01282 ) -stimulated gallbladder mucosal bicarbonate and acid secretion . Gallbladders in anaesthetized cats were perfused with a bicarbonate buffer bubbled with CO2 in air . In 20 experiments P01282 ( 10 microg kg(-1) h(-1) ) and in 10 experiments secretin ( 4 microg kg(-1) h(-1) ) were infused continuously intravenous ( i.v. ) . Hepatic bile and samples from the buffer before and after perfusion of the gallbladder were collected for calculation of ion and fluid transport . During basal conditions a continuous secretion of H+ by the gallbladder mucosa was seen . Intravenous infusion of vasoactive intestinal peptide ( P01282 ) and secretin caused a secretion of bicarbonate from the gallbladder mucosa ( P < 0.01 ) . This secretion was reduced by intraluminal ( i.l. ) acetazolamide ( P < 0.01 ) . Bile flow was enhanced by infusion of P01282 and secretin ( P < 0.01 ) but this stimulated outflow was not affected by i.v. acetazolamide . The presence of CA II in the gallbladder was demonstrated by immunoblotting . Biliary CA activity has an important function in the regulation of P01282 - and secretin-stimulated bicarbonate secretion across the gallbladder mucosa . E3 ubiquitin ligase Q13049 negatively regulates tumor suppressor p53 to promote tumorigenesis . P04637 has a key role in maintaining genomic stability and preventing tumorigenesis through its regulation of cellular stress responses , including apoptosis , cell cycle arrest and senescence . To ensure its proper levels and functions in cells , p53 is tightly regulated mainly through post-translational modifications , such as ubiquitination . Here , we identified E3 ubiquitin ligase Q13049 as a novel p53 target gene and negative regulator to regulate p53-mediated stress responses . In response to stress , such as DNA damage , p53 binds to the p53 responsive element in the promoter of the Q13049 gene and transcriptionally induces the expression of Q13049 in cells . In turn , Q13049 interacts with p53 and promotes p53 degradation through ubiquitination . Thus , Q13049 negatively regulates p53-mediated apoptosis , cell cycle arrest and senescence in response to stress . Q13049 is frequently overexpressed in different types of human tumors . Q13049 overexpression promotes cell oncogenic transformation and tumorigenesis in mice in a largely p53-dependent manner . Taken together , our results demonstrated that as a novel p53 target and a novel negative regulator for p53 , Q13049 has an important role in regulation of p53 and p53-mediated cellular stress responses . Furthermore , our results also revealed that impairing p53 function is a novel mechanism for Q13049 in tumorigenesis . [ RAMPs and G protein coupled receptors ] . RAMPs ( receptor activity-modifying proteins ) were discovered in 1998 as accessory proteins needed to the functionnal activity of P80511 ( calcitonin gene-related peptide ) receptors . Three RAMPs generated by three different genes are known in human , rat and mice . The coding sequences of such genes are described , but as yet , regulation sequences are unknown . RAMPs interact with GPCR ( G protein-coupled receptors ) of class II . In the case of the calcitonin/ P80511 peptide family , RAMPs determine the functionnal specificity of the receptor , glycosylate and translocate the receptor to the cell surface . P80511 receptors are observed in presence of the O60894 /calcitonin receptor-like receptor ( CRLR ) , but the association of O60895 or O60896 with CRLR generates an adrenomedullin receptor . The calcitonin receptor ( CTR ) is translocated alone to the cell surface , but interactions of RAMPs with CTR forms amylin receptors . If RAMPs can interact with glucagon , parathyroid hormone and P01282 /PACAP ( vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide ( VPACR1 ) ) receptors , the functionnal specificity of these receptors remains unaltered . However , the complex VPACR1/ O60895 enhances specifically the phosphoinoside signaling pathway . Prolonged treatment with bicalutamide induces androgen receptor overexpression and androgen hypersensitivity . BACKGROUND : Various hormone refractory prostate cancer cell models have been established with androgen depletion and have helped to clarify the mechanism for the transition into androgen-depletion independent status . However , the mechanism of bicalutamide resistance remains unclear because few cell models have been generated . METHODS : We generated a bicalutamide-resistant subline , LNCaP- O43633 , from LNCaP after prolonged treatment with bicalutamide . Androgen and/or bicalutamide responsiveness for proliferation and prostate-specific antigen ( PSA ) secretion were examined in vitro and in vivo . DB00624 and dihydrotestosterone ( DB02901 ) levels in xenografted tumors were analyzed by liquid chromatography-tandem mass spectrometry . P10275 ( AR ) gene mutation and amplification and AR and pAR(210) expression were determined . RESULTS : LNCaP- O43633 did not grow in an androgen-depleted medium and proliferation was stimulated in a tenfold lower concentration of androgen than that of LNCaP . LNCaP- O43633 grew in castrated male mice , and the DB02901 level in grafted LNCaP- O43633 tumors was 7.7-fold lower than in LNCaP tumors . DB01128 stimulated LNCaP- O43633 proliferation and PSA secretion in vitro and the antitumor activity of bicalutamide against LNCaP- O43633 was weaker than that of LNCaP in vivo . Additional AR mutation and AR gene amplification were not detected in LNCaP- O43633 , but AR and pAR(210) expression and PSA secretion in LNCaP- O43633 were higher than in LNCaP . CONCLUSIONS : DB01128 -resistant LNCaP- O43633 exhibited AR overexpression and hypersensitivity to low levels of androgen . Our data suggests that AR overexpression is a significant mechanism of bicalutamide resistance similar to resistance from chronic androgen depletion . In addition , pAR(210) overexpression could be a potential mechanism for hypersensitivity to low androgen in LNCaP- O43633 . Successful thrombolysis of a stroke with a pulmonary embolism in a young woman . BACKGROUND : Paradoxical embolism is a rare event , accounting for < 2 % of all arterial emboli . The diagnosis is often difficult , and consequences for the patient can be severe . CASE REPORT : We describe the case of a 35-year-old female physician who presented to our Emergency Department ( ED ) in severe hemodynamic compromise , with an altered level of consciousness and major expressive aphasia 1 day after undergoing a leg varicosal stripping procedure under regional anesthesia . She was successfully thrombolyzed with 0.9 mg/kg of Recombinant Tissue P00747 Activator ( rtPA , DB00009 ) and had a full recovery . CONCLUSION : To our knowledge , this is the first description of a case of massive pulmonary embolism associated with a paradoxical stroke related to patent foramen ovale that was thrombolyzed for both conditions with a " neurological dose " of rtPA . Although thrombolysis was completely successful in this case , indications and contraindications should be thoroughly respected . A more conservative approach with anticoagulation , or a more aggressive approach with surgical thrombectomy , can each potentially have a place in particular cases . Intra-arterial catheter-directed thrombolysis and percutaneous embolectomy are additional options to be considered when available , especially if there are contraindications for systemic thrombolysis . Celecoxib with chemotherapy in colorectal cancer . P35354 ( P35354 ) is the enzyme that normally synthesizes prostaglandins during an inflammatory response . Many primary and metastatic cancers express P35354 , and its presence is correlated with tumor angiogenesis , more invasive tumor phenotype , resistance to apoptosis , and systemic immunosuppression . The expression of P35354 is associated with a worse prognosis . Inhibition of prostaglandin synthesis may be beneficial in human malignancy . Regular consumption of nonsteroidal anti-inflammatory drugs ( NSAIDs ) decreases the incidence of , and mortality rate resulting from , a number of types of gastrointestinal cancers . Premalignant colonic lesions regress following the administration of nonspecific P36551 inhibitors , such as sulindac ( DB00605 ) . Advanced solid tumor patients treated with indomethacin ( DB00328 ) survive twice as long as do such patients who receive supportive care alone . The U.S . Food and Drug Administration has approved specific P35354 inhibitors for the treatment of arthritis , pain , and familial adenomatous polyposis . Preclinical studies show that these drugs block angiogenesis , suppress solid tumor metastases , and slow the growth of implanted gastrointestinal cancer cell lines . The P35354 inhibitors have safely and effectively been combined with chemotherapeutic agents in experimental studies . Ongoing clinical trials are currently assessing the potential therapeutic role of P35354 inhibitors in both prevention and treatment of a diverse range of human cancers . Estrogenic chemicals at puberty change ERalpha in the hypothalamus of male and female rats . The effects of two environmental endocrine disruptors , the synthetic pharmaceutical estrogen DB00977 ( EE ) and bisphenol-A ( Q03001 ) , were analysed in male and female rats in a very sensitive developmental period , puberty . Immunohistochemistry was used to evaluate changes in the number of cells expressing estrogen receptors ( P03372 ) in the arcuate nucleus ( ARC ) , ventromedial nucleus ( VMH ) and medial preoptic area ( DB00603 ) of the hypothalamus . Animals were treated during early puberty , from P01160 23 to P01160 30 , with EE and Q03001 given orally every day . They were then sacrificed and perfused on P01160 37 or P01160 90 , and blood and brains were collected for hormonal determination ( testosterone and estradiol ) and immunohistochemistry ( estrogen receptors , ER ) . At P01160 37 , ER-labelled neurons were higher in males than in females in the ARC and DB00603 . EE and Q03001 increased ER-labelled neurons in the ARC and DB00603 . At P01160 90 , females showed higher ER-labelled neurons in the VMH . EE and Q03001 increased ER-labelled neurons in the DB00603 in females . EE increased testosterone in males at P01160 37 and estradiol in females at P01160 90 . These results indicate the ability of estrogenic chemicals to change the reproductive neural circuits during puberty in male and female rats . Role of presynaptic serotonergic receptors on the mechanism of action of P08908 and P28222 agonists on masculine sexual behaviour : physiological and pharmacological implications . In order to establish whether the P08908 or the 5HT1B agonists , 8-OH-DPAT or TFMPP , produce their facilitatory or inhibitory actions on masculine sexual behaviour via a mechanism involving : ( a ) the serotonin synthesis or release ; ( b ) the stimulation of presynaptic receptors , or ( c ) the stimulation of somatodendritic receptors , three series of experiments were performed . The administration of the serotonin synthesis inhibitor , p-chlorophenylalanine ( p- P15085 , 300 mg/kg x 3 days ) , facilitated sexual behaviour but does not interfere neither with the inhibitory nor with the facilitatory effects of TFMPP ( 0.5 mg/kg ) or 8-OH-DPAT ( 0.5 mg/kg ) , respectively . The icv or the intraraphé administration of the serotonergic neurotoxin , 5,7-dihydroxytryptamine ( 5,7- DB02901 ) , slightly stimulated masculine sexual behaviour and produced a decrease in serotonin and its metabolite levels . In lesioned animals TFMPP ( 0.5 mg/kg ) resulted in an inhibitory effect reflected as a prolongation of the ejaculation latency . The inhibitory effect of this drug on mounting behaviour was not observed in 5,7- DB02901 treated rats . In lesioned animals 8-OH-DPAT ( 0.5 mg/kg ) produced the same facilitatory effect . Present data indicate that serotonergic postsynaptic receptors mediate both the inhibitory and the facilitatory actions of TFMPP or 8-OH-DPAT in copulation . All data further support the idea that endogenous serotonin acts via the stimulation of P28222 receptors to induce its inhibitory effects on masculine sexual behaviour . Molecular mechanisms of low dose ionizing radiation-induced hormesis , adaptive responses , radioresistance , bystander effects , and genomic instability . PURPOSES : To review research progress on the molecular mechanisms of low dose ionizing radiation ( LDIR ) -induced hormesis , adaptive responses , radioresistance , bystander effects , and genomic instability in order to provide clues for therapeutic approaches to enhance biopositive effects ( defined as radiation-induced beneficial effects to the organism ) , and control bionegative effects ( defined as radiation-induced harmful effects to the organism ) and related human diseases . CONCLUSIONS : Experimental studies have indicated that Ataxia telangiectasia-mutated ( Q13315 ) , extracellular signal-related kinase ( P29323 ) , mitogen-activated protein kinase ( MAPK ) , phospho-c-Jun NH(2)-terminal kinase ( JNK ) and protein 53 ( P04637 ) -related signal transduction pathways may be involved in LDIR-induced hormesis ; MAPK , P04637 may be important for adaptive response ; Q13315 , cyclooxygenase-2 ( P35354 ) , P29323 , JNK , reactive oxygen species ( ROS ) , P04637 for radioresistance ; P35354 , P29323 , MAPK , ROS , tumor necrosis factor receptor alpha ( TNFα ) for LDIR-induced bystander effect ; whereas Q13315 , P29323 , MAPK , P04637 , ROS , TNFα-related signal transduction pathways are involved in LDIR-induced genomic instability . These results suggest that different manifestations of LDIR-induced cellular responses may have different signal transduction pathways . On the other hand , LDIR-induced different responses may also share the same signal transduction pathways . For instance , P04637 has been involved in LDIR-induced hormesis , adaptive response , radioresistance and genomic instability . Current data therefore suggest that caution should be taken when designing therapeutic approaches using LDIR to induce beneficial effects in humans . Effects of systemic injections of vilazodone , a selective serotonin reuptake inhibitor and serotonin 1A receptor agonist , on anxiety induced by predator stress in rats . We examined the effect of DB06684 , a selective serotonin reuptake inhibitor ( SSRI ) and serotonin 1A ( 5-HT(1A) ) receptor agonist [ Bartoszyk , G.D. , Hegenbart , R. , Ziegler , H. , 1997. P50402 68843 , a serotonin reuptake inhibitor with selective presynaptic P08908 receptor agonistic properties. Eur. J. Pharmacol. 322 , 147-153. ] , on change in affect following predator stress . DB06684 and vehicle injection ( intraperitoneal ) occurred either 10 min after predator stress ( prophylactic testing ) , or 90 min prior to behavioral testing for the effects of predator stress ( therapeutic testing ) . Predator stress involved unprotected exposure of rats to a domestic cat . Behavioral effects of stress were evaluated with hole board , plus-maze , and acoustic startle tests 1 week after stress . Predator stress increased anxiety-like behavior in the plus-maze and elevated response to acoustic startle . In prophylactic testing , DB06684 affected stress potentiation of startle at doses above 5 mg/kg . DB06684 increased stress elevation of startle at 10 mg/kg . Higher doses of DB06684 ( 20 and 40 mg/kg ) blocked stress potentiation of startle . In contrast , DB06684 had no effect on stress potentiation of anxiety in the plus-maze . In therapeutic testing , DB06684 increased stress elevation of startle at all doses . In contrast , therapeutic DB06684 had no effect on stress potentiation of anxiety in the plus-maze . Taken together , the data suggest a prophylactic potential for DB06684 in the treatment of changes in hypervigilance following severe stress . P10997 -driven metabolic reprogramming induces regression of p53-deficient tumours in vivo . P04637 is commonly altered in human cancer , and Tp53 reactivation suppresses tumours in vivo in mice ( P04637 and Tp53 are also known as p53 ) . This strategy has proven difficult to implement therapeutically , and here we examine an alternative strategy by manipulating the p53 family members , Tp63 and Tp73 ( also known as p63 and p73 , respectively ) . The acidic transactivation-domain-bearing ( TA ) isoforms of p63 and p73 structurally and functionally resemble p53 , whereas the ΔN isoforms ( lacking the acidic transactivation domain ) of p63 and p73 are frequently overexpressed in cancer and act primarily in a dominant-negative fashion against p53 , TAp63 and TAp73 to inhibit their tumour-suppressive functions . The p53 family interacts extensively in cellular processes that promote tumour suppression , such as apoptosis and autophagy , thus a clear understanding of this interplay in cancer is needed to treat tumours with alterations in the p53 pathway . Here we show that deletion of the ΔN isoforms of p63 or p73 leads to metabolic reprogramming and regression of p53-deficient tumours through upregulation of P10997 , the gene that encodes amylin , a 37-amino-acid peptide co-secreted with insulin by the β cells of the pancreas . We found that P10997 is causally involved in this tumour regression and that amylin functions through the calcitonin receptor ( CalcR ) and receptor activity modifying protein 3 ( O60896 ) to inhibit glycolysis and induce reactive oxygen species and apoptosis . DB01278 , a synthetic analogue of amylin that is currently used to treat type 1 and type 2 diabetes , caused rapid tumour regression in p53-deficient thymic lymphomas , representing a novel strategy to target p53-deficient cancers .