bcl 2 genes

Summary

Summary: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.

Top Publications

  1. Dexheimer T, Sun D, Hurley L. Deconvoluting the structural and drug-recognition complexity of the G-quadruplex-forming region upstream of the bcl-2 P1 promoter. J Am Chem Soc. 2006;128:5404-15 pubmed
  2. Dai J, Chen D, Jones R, Hurley L, Yang D. NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region. Nucleic Acids Res. 2006;34:5133-44 pubmed
    ..Significantly, the distinct major BCL2 promoter G-quadruplex structure suggests that it can be specifically involved in gene modulation and can be an attractive target for pathway-specific drug design. ..
  3. O Keeffe M, Grumont R, Hochrein H, Fuchsberger M, Gugasyan R, Vremec D, et al. Distinct roles for the NF-kappaB1 and c-Rel transcription factors in the differentiation and survival of plasmacytoid and conventional dendritic cells activated by TLR-9 signals. Blood. 2005;106:3457-64 pubmed
    ..Collectively, these findings establish that NF-kappaB1 and c-Rel, while largely dispensable for TLR-9-induced cDC activation, are critical for regulating differentiation and survival programs during pDC activation. ..
  4. Dai J, Dexheimer T, Chen D, Carver M, Ambrus A, Jones R, et al. An intramolecular G-quadruplex structure with mixed parallel/antiparallel G-strands formed in the human BCL-2 promoter region in solution. J Am Chem Soc. 2006;128:1096-8 pubmed
    ..This predominant bcl-2 G-quadruplex represents an attractive novel target for the design of new anticancer drugs that specifically modulate bcl-2 gene expression. ..
  5. Knezevich S, Ludkovski O, Salski C, Lestou V, Chhanabhai M, Lam W, et al. Concurrent translocation of BCL2 and MYC with a single immunoglobulin locus in high-grade B-cell lymphomas. Leukemia. 2005;19:659-63 pubmed
    ..Molecular cytogenetic investigation is essential to identify cases of high-grade leukaemia/lymphoma with concurrent translocations affecting the BCL2 and MYC loci. ..
  6. Lee J, Lee T, Park J, Kwon T. Se-methylselenocysteine sensitized TRAIL-mediated apoptosis via down-regulation of Bcl-2 expression. Int J Oncol. 2009;34:1455-60 pubmed
    ..Thus, selenium-based dietary compounds may help to overcome resistance to TRAIL-mediated apoptosis in renal cancer cells. ..
  7. He D, Fang B. Small hairpin RNA targeting at Bcl-2 increases cytarabine-induced apoptosis in Raji cells. Acta Biochim Biophys Sin (Shanghai). 2009;41:131-6 pubmed
    ..05), compared with either control shRNA/Ara-C combination or Ara-C-treated cells alone. Our results suggest that the shRNA against Bcl-2 mRNA could increase Ara-C-induced apoptosis in Raji cells. ..
  8. Thomadaki H, Scorilas A. Molecular profile of the BCL2 family of the apoptosis related genes in breast cancer cells after treatment with cytotoxic/cytostatic drugs. Connect Tissue Res. 2008;49:261-4 pubmed publisher
    ..In the present review, we describe current knowledge of the molecular profile of the classical and novel members of the BCL2 family of genes as a response of breast cancer cells to cytotoxic/cytostatic drugs. ..
  9. Libra M, Gloghini A, Malaponte G, Gangemi P, De Re V, Cacopardo B, et al. Association of t(14;18) translocation with HCV infection in gastrointestinal MALT lymphomas. J Hepatol. 2008;49:170-4 pubmed publisher
    ..Our data support the notion that among gastrointestinal MALT lymphomas, t(14;18)-(IgH;Bcl-2) translocation clusters in HCV-positive patients sustaining the role of HCV infection in the lymphoma development. ..

More Information

Publications62

  1. Stoos Veić T, Livun A, Ajdukovic R, Pejsa V, Jaksic O, Kusec R. Detection of t(14;18) by PCR of IgH/BCL2 fusion gene in follicular lymphoma from archived cytological smears. Coll Antropol. 2010;34:425-9 pubmed
    ..For patients with detectable baseline molecular marker, PCR is a highly suitable method for detection of bone marrow involvement and monitoring MRD. ..
  2. Takahashi S, Yoshimura Y, Yamamoto T, Wakita M. Cellular expression of Bcl-2 and Bax in atrophic submandibular glands of rats. Int J Exp Pathol. 2008;89:303-8 pubmed publisher
    ..These observations suggest that Bcl-2 inhibits duct cell apoptosis and Bax promotes apoptosis of acinar cells during atrophy of submandibular glands. ..
  3. Chang H, Yoon G, Park J, Kim M, Baek M, Kim N, et al. Induction of apoptosis by the licochalcone E in endothelial cells via modulation of NF-kappaB and Bcl-2 Family. Biol Pharm Bull. 2007;30:2290-3 pubmed
    ..In addition, the Lico-E treatment caused a change in the Bax/Bcl-2 ratio that favored apoptosis. These results suggest that Lico-E induces endothelial cell apoptosis by modulating NF-kappaB and the Bcl-2 family. ..
  4. Karowicz Bilinska A, Szczerba A, Kowalska Koprek U, Nawrocka Kunecka A. The evaluation of selected indices of apoptosis in placentas from pregnancies complicated by fetal growth restriction. Ginekol Pol. 2007;78:521-6 pubmed
    ..63 +/- 2.24. 1. Apoptosis in trophoblast is lower in normal pregnancy than in FGR. 2. Increased expression of pro-apoptotic proteins in placenta might be one of the reason for FGR development. ..
  5. Kassi E, Sourlingas T, Spiliotaki M, Papoutsi Z, Pratsinis H, Aligiannis N, et al. Ursolic acid triggers apoptosis and Bcl-2 downregulation in MCF-7 breast cancer cells. Cancer Invest. 2009;27:723-33 pubmed publisher
    ..UA had no effect on GRE- or TRE-driven gene expression. In summary, UA is a GR modulator and may be considered as a potential anticancer agent in breast cancer. ..
  6. Agas D, Marchetti L, Menghi G, Materazzi S, Materazzi G, Capacchietti M, et al. Anti-apoptotic Bcl-2 enhancing requires FGF-2/FGF receptor 1 binding in mouse osteoblasts. J Cell Physiol. 2008;214:145-52 pubmed
    ..In conclusion, we report a novel mechanism in which PGF2alpha induces FGF-2 binding to its specific cell surface receptor 1 leading to a cascade pathway that culminates with increased mouse osteoblast survival. ..
  7. Wilson K, Sehn L, Berry B, Chhanabhai M, Fitzgerald C, Gill K, et al. CHOP-R therapy overcomes the adverse prognostic influence of BCL-2 expression in diffuse large B-cell lymphoma. Leuk Lymphoma. 2007;48:1102-9 pubmed
    ..The addition of rituximab to CHOP chemotherapy negates the adverse prognostic influence of BCL-2 protein expression on progression free and overall survival in DLBCL. ..
  8. Ihemelandu C, Leffall L, DeWitty R, Naab T, Mezghebe H, Makambi K, et al. Molecular breast cancer subtypes in premenopausal African-American women, tumor biologic factors and clinical outcome. Ann Surg Oncol. 2007;14:2994-3003 pubmed
    ..31). The high prevalence of the basal-cell-like subtype in young premenopausal African-American women aged <35 years may contribute to the poorer prognosis observed in this cohort of African-American women. ..
  9. Karube K, Guo Y, Suzumiya J, Sugita Y, Nomura Y, Yamamoto K, et al. CD10-MUM1+ follicular lymphoma lacks BCL2 gene translocation and shows characteristic biologic and clinical features. Blood. 2007;109:3076-9 pubmed
    ..Our results indicate that CD10-MUM1+ FL is different from typical FL with respect to biologic and clinical features. ..
  10. Li Y, Liu B, Sailhamer E, Yuan Z, Shults C, Velmahos G, et al. Cell protective mechanism of valproic acid in lethal hemorrhagic shock. Surgery. 2008;144:217-24 pubmed publisher
    ..This study investigated whether VPA treatment works through the beta-catenin survival pathways...
  11. Lin P, Huang Y, John J, Chang Y, Yuan C, Chen W, et al. Iridovirus Bcl-2 protein inhibits apoptosis in the early stage of viral infection. Apoptosis. 2008;13:165-76 pubmed
    ..Taken together, these results demonstrate that GIV inhibits the promotion of apoptosis by GK cells, which is mediated by the immediate early expressed viral Bcl gene. ..
  12. Yang N, Zhu X, Chen L, Li S, Ren D. Oral administration of attenuated S. typhimurium carrying shRNA-expressing vectors as a cancer therapeutic. Cancer Biol Ther. 2008;7:145-51 pubmed
    ..These results suggest that bacteria mediated RNAi may be a new potent approach to the treatment of cancers. ..
  13. Hostmann A, Jasse K, Schulze Tanzil G, Robinson Y, Oberholzer A, Ertel W, et al. Biphasic onset of splenic apoptosis following hemorrhagic shock: critical implications for Bax, Bcl-2, and Mcl-1 proteins. Crit Care. 2008;12:R8 pubmed publisher
  14. Thomadaki H, Talieri M, Scorilas A. Prognostic value of the apoptosis related genes BCL2 and BCL2L12 in breast cancer. Cancer Lett. 2007;247:48-55 pubmed
    ..Multivariate analysis revealed that BCL2 and BCL2L12 might be used as independent prognostic biomarkers in breast cancer. ..
  15. Duval A, Olaru D, Campos L, Flandrin P, Nadal N, Guyotat D. Expression and prognostic significance of heat-shock proteins in myelodysplastic syndromes. Haematologica. 2006;91:713-4 pubmed
  16. Taratula O, Garbuzenko O, Kirkpatrick P, Pandya I, Savla R, Pozharov V, et al. Surface-engineered targeted PPI dendrimer for efficient intracellular and intratumoral siRNA delivery. J Control Release. 2009;140:284-93 pubmed publisher
    ..In addition, in vivo body distribution data confirmed high specificity of the proposed targeting delivery approach which created the basis for the prevention of adverse side effects of the treatment on healthy organs. ..
  17. Gutkowska J, Broderick T, Bogdan D, Wang D, Lavoie J, Jankowski M. Downregulation of oxytocin and natriuretic peptides in diabetes: possible implications in cardiomyopathy. J Physiol. 2009;587:4725-36 pubmed publisher
    ..05). In conclusion, downregulation of the OT-NPs-NO system occurs in the heart of the young db/db mouse. Exercise training was not effective in reversing the defect, suggesting impairment of this cardiac protective system in diabetes. ..
  18. Wennicke K, Debierre Grockiego F, Wichmann D, Brattig N, Pankuweit S, Maisch B, et al. Glycosylphosphatidylinositol-induced cardiac myocyte death might contribute to the fatal outcome of Plasmodium falciparum malaria. Apoptosis. 2008;13:857-66 pubmed publisher
    ..Our studies performed in vitro and in mice suggest that the GPI could be responsible for cardiomyocyte apoptosis that occurred in this patient. Plasmodium falciparum GPI-induced apoptosis might participate in the lethality of malaria. ..
  19. Tan S, Bakker A, Semeins C, Kuijpers Jagtman A, Klein Nulend J. Inhibition of osteocyte apoptosis by fluid flow is mediated by nitric oxide. Biochem Biophys Res Commun. 2008;369:1150-4 pubmed publisher
    ..This suggests that PFF inhibits osteocyte apoptosis via alterations in Bcl-2 and caspase-3 gene expression, which is at least partially regulated by NO. ..
  20. Rowland S, Depersis C, Torres R, Pelanda R. Ras activation of Erk restores impaired tonic BCR signaling and rescues immature B cell differentiation. J Exp Med. 2010;207:607-21 pubmed publisher
    ..These results strongly suggest that tonic BCR signaling mediates the differentiation of immature into transitional and mature B cells via activation of Erk, likely through a pathway requiring Ras. ..
  21. Guan Q, Nguan C, Du C. Expression of transforming growth factor-beta1 limits renal ischemia-reperfusion injury. Transplantation. 2010;89:1320-7 pubmed publisher
    ..In mice, TGF-beta1 deficiency results in more prone to IRI. These data imply that TGF-beta1 may act as a feedback survival factor in the resistance to kidney injury and maintenance of epithelium homeostasis. ..
  22. Raghavan S, Lieber M. DNA structures at chromosomal translocation sites. Bioessays. 2006;28:480-94 pubmed
    ..Here we summarize these findings and integrate them with other recent data for non-B structures at sites of consistent constitutional chromosomal translocations. ..
  23. Chen C, Hsu M, Kuo S, Lai Y, Chung J, Huang L. (2E)-N,N-dibutyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide induces apoptosis and cell cycle arrest in HL-60 cells. Anticancer Res. 2007;27:343-9 pubmed
    ..After G2/M-phase arrest, cells underwent apoptosis via significant down-regulation of Bcl-2 expression. These results enhance our understanding of the mechanisms of action of compound 8-mediated anticancer effects. ..
  24. Tong W, Ding X, Talamonti M, Bell R, Adrian T. Leukotriene B4 receptor antagonist LY293111 induces S-phase cell cycle arrest and apoptosis in human pancreatic cancer cells. Anticancer Drugs. 2007;18:535-41 pubmed
    ..LY293111 also induces S-phase arrest with downregulation of CDK2, cyclin A and cyclin E. Blockade of leukotriene B4 metabolic pathway may provide a novel treatment for human pancreatic cancer. ..
  25. Wang Q, Huang Y, Ni Y, Wang H, Hou Y. siRNA targeting midkine inhibits gastric cancer cells growth and induces apoptosis involved caspase-3,8,9 activation and mitochondrial depolarization. J Biomed Sci. 2007;14:783-95 pubmed
    ..MK siRNA may be a promising novel and potential therapeutic strategy for the treatment of gastric cancers. ..
  26. Henshall D, Murphy B. Modulators of neuronal cell death in epilepsy. Curr Opin Pharmacol. 2008;8:75-81 pubmed
    ..These findings may yield potentially valuable adjunctive neuroprotective or anti-epileptogenic strategies. ..
  27. Bishnupuri K, Luo Q, Korzenik J, Henderson J, Houchen C, Anant S, et al. Dysregulation of Reg gene expression occurs early in gastrointestinal tumorigenesis and regulates anti-apoptotic genes. Cancer Biol Ther. 2006;5:1714-20 pubmed
    ..Furthermore, increased expression of Reg genes, specifically Reg IV contribute to adenoma formation and lead to increased resistance to apoptotic cell death in CRC. ..
  28. Tien C, Wen F, Hsieh M. The polyglutamine-expanded protein ataxin-3 decreases bcl-2 mRNA stability. Biochem Biophys Res Commun. 2008;365:232-8 pubmed
    ..5-fold faster than that in COS7-MJD26-GFP. Our study provides evidence, for the first time, that dysfunction of mRNA stability resulted from the presence of mutant ataxin-3. ..
  29. Koka S, Das A, Zhu S, Durrant D, Xi L, Kukreja R. Long-acting phosphodiesterase-5 inhibitor tadalafil attenuates doxorubicin-induced cardiomyopathy without interfering with chemotherapeutic effect. J Pharmacol Exp Ther. 2010;334:1023-30 pubmed publisher
  30. Pedeboscq S, L Azou B, Passagne I, De Giorgi F, Ichas F, Liguoro D, et al. Anticancer drugs exert differential apoptotic and cytotoxic effects on glioblastoma primary cultures with various EGFR and bcl-2 profiles. J Exp Ther Oncol. 2009;8:105-16 pubmed
    ..Moreover, the characterization of patients' cells for EGFR and bcl-2 status could constitute an interest, with the evaluation of other markers, in the study of expected chemotherapy response. ..
  31. Bonovolias I, Tsiftsoglou A. Hemin counteracts the repression of Bcl-2 and NrF2 genes and the cell killing induced by imatinib in human Bcr-Abl(+) CML cells. Oncol Res. 2009;17:535-47 pubmed
  32. Obermann E, Csato M, Dirnhofer S, Tzankov A. BCL2 gene aberration as an IPI-independent marker for poor outcome in non-germinal-centre diffuse large B cell lymphoma. J Clin Pathol. 2009;62:903-7 pubmed publisher
    ..It may be helpful to asses BCL2 gene abnormalities by FISH in addition to assessing established parameters for individual risk estimation in DLBCL. ..
  33. Filali M, Frydman N, Belot M, Hesters L, Gaudin F, Tachdjian G, et al. Oocyte in-vitro maturation: BCL2 mRNA content in cumulus cells reflects oocyte competency. Reprod Biomed Online. 2009;19 Suppl 4:4309 pubmed
    ..140 versus 0.075; P = 0.03). These results suggest that BCL2 expression is strongly associated with the ability of oocytes to complete nuclear maturation and to be fertilized. ..
  34. Pervez S, Nasir M, Moatter T, Ahsan A, Haq A, Siddiqui T. Characterization of genetic lesions in apoptosis-regulating and proliferation control genes in diffuse large B-cell non-Hodgkin's lymphoma. J Cancer Res Ther. 2009;5:254-62 pubmed publisher
    ..Our data suggest that simple p53 protein expression by IHC at the time of diagnosis may help to identify high-risk patients, who may benefit with more aggressive and newer treatments in addition to standard CHOP. ..
  35. Robert F, Carrier M, Rawe S, Chen S, Lowe S, Pelletier J. Altering chemosensitivity by modulating translation elongation. PLoS ONE. 2009;4:e5428 pubmed publisher
    ..Our results indicate that depleting short-lived pro-survival factors by inhibiting their synthesis could achieve a therapeutic response in tumors harboring PTEN/AKT/mTOR pathway mutations. ..
  36. del Toro M, Bucek P, Aviñó A, Jaumot J, Gonzalez C, Eritja R, et al. Targeting the G-quadruplex-forming region near the P1 promoter in the human BCL-2 gene with the cationic porphyrin TMPyP4 and with the complementary C-rich strand. Biochimie. 2009;91:894-902 pubmed publisher
    ..7) M(-1) (at pH 7.1). Finally, the pH-induced formation of quadruplex structures from the Watson-Crick double-helix is characterized. ..
  37. Costes S, Broca C, Bertrand G, Lajoix A, Bataille D, Bockaert J, et al. ERK1/2 control phosphorylation and protein level of cAMP-responsive element-binding protein: a key role in glucose-mediated pancreatic beta-cell survival. Diabetes. 2006;55:2220-30 pubmed
    ..Our results indicate that ERK1 and -2 control the phosphorylation and protein level of CREB and play a key role in glucose-mediated pancreatic beta-cell survival. ..
  38. Liu X, Zhang D, Li Y, Xiong J, He D, Lin T, et al. Di-(2-ethylhexyl) phthalate upregulates ATF3 expression and suppresses apoptosis in mouse genital tubercle. J Occup Health. 2009;51:57-63 pubmed
    ..These results suggest that DEHP may induce external genital defects via a mechanism involving apoptosis, which might correlate with the regulation of ATF3 and P53 expressions. ..
  39. Whitecross K, Alsop A, Cluse L, Wiegmans A, Banks K, Coomans C, et al. Defining the target specificity of ABT-737 and synergistic antitumor activities in combination with histone deacetylase inhibitors. Blood. 2009;113:1982-91 pubmed publisher
    ..Our studies provide important preclinical data on the binding specificity of ABT-737 and its usefulness against primary hematologic malignancies when used as a single agent and in combination with HDACi. ..
  40. Wang X, He Y. [Construction of a lentiviral vector carrying human bcl-2 gene and its expression in human ovarian granulosa cells]. Nan Fang Yi Ke Da Xue Xue Bao. 2008;28:1856-9 pubmed
    ..The recombinant lentivirus GC-FU-bcl-2 has been successfully constructed, which is capable of delivering the target gene bcl-2 into human ovarian GCs for its stable expression. ..
  41. Jiang H, Zhang S, Zhao T. A new method to make nuclei or cell microarrays. Diagn Mol Pathol. 2006;15:109-14 pubmed
    ..6-mm-diameter core. The microarrays were successfully used in fluorescence in situ hybridization, mRNA in situ hybridization, and cytohistochemical staining. ..
  42. Yao J, Duan L, Fan M, Wu X. NF-kappaB signaling pathway is involved in growth inhibition, G2/M arrest and apoptosis induced by Trichostatin A in human tongue carcinoma cells. Pharmacol Res. 2006;54:406-13 pubmed
    ..Overall, our results indicate inhibition of NF-kappaB activation contributes, at least partially, to the antitumour activity of TSA in human tongue carcinoma cells. ..
  43. Zhao L, Yano T, Osuga Y, Nakagawa S, Oishi H, Wada Hiraike O, et al. Cellular mechanisms of growth inhibition of human endometrial cancer cell line by an antagonist of growth hormone-releasing hormone. Int J Oncol. 2008;32:593-601 pubmed
  44. Morel P, Gaulard P, Gisselbrecht C, Ferme C, Salles G, Tilly H, et al. Autologous stem-cell transplantation as consolidation therapy for diffuse large B-cell lymphoma patients with overexpression of bcl-2 protein. Results of the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trial LNH98-B2. Ann Oncol. 2008;19:560-5 pubmed
  45. Yang X, Zheng X, Liu W, Feng J. Bcl-2 gene therapy for apoptosis following traumatic brain injury. Chin J Traumatol. 2006;9:276-81 pubmed
    ..Bcl-2 fusion protein can suppress apoptosis and promote cell survival. Moreover, the behavior recovery of the injured animal is promoted. Bcl-2 fusion protein provides a way to track the target cells in vivo. ..
  46. O Brien S, Moore J, Boyd T, Larratt L, Skotnicki A, Koziner B, et al. Randomized phase III trial of fludarabine plus cyclophosphamide with or without oblimersen sodium (Bcl-2 antisense) in patients with relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2007;25:1114-20 pubmed
  47. Mukherjee S, Ray D, Falchi M, Bertelli A, Pini E, Das D. Cardioprotection with the parrodiene 2,4,6-octatrienal and its potassium salt through activation of the Akt-Bcl-2 survival pathway. J Nat Prod. 2009;72:871-5 pubmed publisher
    ..These agents also reduced myocardial ischemic reperfusion injury presumably by reducing oxidative stress and activating the survival signal through the Akt-Bcl-2 pathway. ..
  48. Choi B, Kim Y, Kwon P, Lee S, Kang S, Kim M, et al. 4-1BB functions as a survival factor in dendritic cells. J Immunol. 2009;182:4107-15 pubmed publisher
    ..These results demonstrate that 4-1BB on DCs controls the duration, DC-T interaction, and, therefore, immunogenicity. ..
  49. Li J, Li Q, Gao D, Han Z, Li K. Antitumor effects of total alkaloids isolated from Solanum nigrum in vitro and in vivo. Pharmazie. 2008;63:534-8 pubmed
    ..These results suggested that SNL-A may be a potential, natural apoptosis-inducing agent for cervical cancer. ..
  50. Hamada N, Hara T, Omura Minamisawa M, Funayama T, Sakashita T, Sora S, et al. The survival of heavy ion-irradiated Bcl-2 overexpressing radioresistant tumor cells and their progeny. Cancer Lett. 2008;268:76-81 pubmed publisher
    ..The incidence of delayed reproductive death increased with LET irrespective of Bcl-2 overexpression, suggesting that Bcl-2 overexpression may not facilitate heavy ion-induced genomic instability. ..
  51. Lu C, Shervington A. Chemoresistance in gliomas. Mol Cell Biochem. 2008;312:71-80 pubmed publisher
    ..An improved understanding of MDR may lead to a combined treatment, targeting both CSCs and their protective MDR phenotypes leading eventually to attractive strategies for the treatment of gliomas. ..
  52. Chen X, Cao L, She M, Wang Q, Huang X, Fu X. Gli-1 siRNA induced apoptosis in Huh7 cells. World J Gastroenterol. 2008;14:582-9 pubmed
    ..Combination Gli-1 siRNA with chemotherapeutic drug could represent a more promising strategy against HCC. The effects of the strategies need further investigation in vivo and may have potential clinical application. ..
  53. Skommer J, Brittain T, Raychaudhuri S. Bcl-2 inhibits apoptosis by increasing the time-to-death and intrinsic cell-to-cell variations in the mitochondrial pathway of cell death. Apoptosis. 2010;15:1223-33 pubmed publisher
    ..This is an unanticipated facet of cancer chemoresistance. ..