Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Drug Repurposing in the Development of Anticancer Agents

Author(s): Sureyya Olgen* and Lakshmi P. Kotra*

Volume 26, Issue 28, 2019

Page: [5410 - 5427] Pages: 18

DOI: 10.2174/0929867325666180713155702

Price: $65

Abstract

Background: Research into repositioning known drugs to treat cancer other than the originally intended disease continues to grow and develop, encouraged in part, by several recent success stories. Many of the studies in this article are geared towards repurposing generic drugs because additional clinical trials are relatively easy to perform and the drug safety profiles have previously been established.

Objective: This review provides an overview of anticancer drug development strategies which is one of the important areas of drug restructuring.

Methods: Repurposed drugs for cancer treatments are classified by their pharmacological effects. The successes and failures of important repurposed drugs as anticancer agents are evaluated in this review.

Results and Conclusion: Drugs could have many off-target effects, and can be intelligently repurposed if the off-target effects can be employed for therapeutic purposes. In cancer, due to the heterogeneity of the disease, often targets are quite diverse, hence a number of already known drugs that interfere with these targets could be deployed or repurposed with appropriate research and development.

Keywords: Drug repurposing, anticancer, drug development, recent applications, clinical trials, off-target effects.

« Previous
[1]
Nosengo, N. New tricks for old drugs. Nature, 2016, 534, 314-316.
[http://dx.doi.org/10.1038/534314a] [PMID: 27306171]
[2]
Ashburn, T.T.; Thor, K.B. Drug repositioning: identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov., 2004, 3(8), 673-683.
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[3]
Chen, H.; Wu, J.; Gao, Y.; Chen, H.; Zhou, J. Scaffold repurposing of old drugs towards new cancer drug discovery. Curr. Top. Med. Chem., 2016, 16(19), 2107-2114.
[http://dx.doi.org/10.2174/1568026616666160216155556] [PMID: 26881709]
[4]
Andronis, C.; Sharma, A.; Virvilis, V.; Deftereos, S.; Persidis, A. Literature mining, ontologies and information visualization for drug repurposing. Brief. Bioinform., 2011, 12(4), 357-368.
[http://dx.doi.org/10.1093/bib/bbr005] [PMID: 21712342]
[5]
March-Vila, E.; Pinzi, L.; Sturm, N.; Tinivella, A.; Engkvist, O.; Chen, H.; Rastelli, G. On the Integration of in silico drug design methods for drug repurposing. Front. Pharmacol., 2017, 8, 298-304.
[http://dx.doi.org/10.3389/fphar.2017.00298] [PMID: 28588497]
[6]
Chopra, G.; Samudrala, R. Exploring polypharmacology in drug discovery and repurposing using the CANDO platform. Curr. Pharm. Des., 2016, 22(21), 3109-3123.
[http://dx.doi.org/10.2174/1381612822666160325121943] [PMID: 27013226]
[7]
Reddy, A.S.; Zhang, S. Polypharmacology: Drug discovery for the future. Expert Rev. Clin. Pharmacol., 2013, 6(1), 41-47.
[http://dx.doi.org/10.1586/ecp.12.74] [PMID: 23272792]
[8]
Turner, N.; Zeng, X-Y.; Osborne, B.; Rogers, S.; Ye, J-M. Repurposing drugs to target the diabetes epidemic. Trends Pharmacol. Sci., 2016, 37(5), 379-389.
[http://dx.doi.org/10.1016/j.tips.2016.01.007] [PMID: 26900045]
[9]
Huang, J.; Zhao, D.; Liu, Z.; Liu, F. Repurposing psychiatric drugs as anticancer agents. Cancer Lett., 2018, 419, 257-265.
[http://dx.doi.org/10.1016/j.cancet.2018.01.058] [PMID: 29414306]
[10]
Zhou, S.; Wang, F.; Hsieh, T-C.; Wu, J.M.; Wu, E. Thalidomide-a notorious sedative to a wonder anticancer drug. Curr. Med. Chem., 2013, 20(33), 4102-4108.
[http://dx.doi.org/10.2174/09298673113209990198] [PMID: 23931282]
[11]
Stephens, T.D.; Fillmore, B.J. Hypothesis: thalidomide embryopathy-proposed mechanism of action. Teratology, 2000, 61(3), 189-195.
[http://dx.doi.org/10.1002/(SICI)1096-9926(200003)61:3<189:AID-TERA6>3.0.CO;2-W] [PMID: 10661908]
[12]
Hideshima, T.; Raje, N.; Richardson, P.G.; Anderson, K.C. A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma. Ther. Clin. Risk Manag., 2008, 4(1), 129-136.
[http://dx.doi.org/10.2147/TCRM.S1445] [PMID: 18728702]
[13]
Galustian, C.; Dalgleish, A. Lenalidomide: a novel anticancer drug with multiple modalities. Expert Opin. Pharmacother., 2009, 10(1), 125-133.
[http://dx.doi.org/10.1517/14656560802627903] [PMID: 19236186]
[14]
Richardson, P.G.; Weller, E.; Lonial, S.; Jakubowiak, A.J.; Jagannath, S.; Raje, N.S.; Avigan, D.E.; Xie, W.; Ghobrial, I.M.; Schlossman, R.L.; Mazumder, A.; Munshi, N.C.; Vesole, D.H.; Joyce, R.; Kaufman, J.L.; Doss, D.; Warren, D.L.; Lunde, L.E.; Kaster, S.; Delaney, C.; Hideshima, T.; Mitsiades, C.S.; Knight, R.; Esseltine, D-L.; Anderson, K.C. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood, 2010, 116(5), 679-686.
[http://dx.doi.org/10.1182/blood-2010-02-268862] [PMID: 20385792]
[15]
Licht, J.D.; Shortt, J.; Johnstone, R. From anecdote to targeted therapy: the curious case of thalidomide in multiple myeloma. Cancer Cell, 2014, 25(1), 9-11.
[http://dx.doi.org/10.1016/j.ccr.2013.12.019] [PMID: 24434206]
[16]
Ríos-Tamayo, R.; Martín-García, A.; Alarcón-Payer, C.; Sánchez-Rodríguez, D.; de la Guardia, A.M.D.V.D.; García Collado, C.G.; Jiménez Morales, A.; Jurado Chacón, M.; Cabeza Barrera, J. Pomalidomide in the treatment of multiple myeloma: design, development and place in therapy. Drug Des. Devel. Ther., 2017, 11, 2399-2408.
[http://dx.doi.org/10.2147/DDDT.S115456] [PMID: 28860711]
[17]
Agarwala, S.S.; Kirkwood, J.M. Temozolomide, a novel alkylating agent with activity in the central nervous system, may improve the treatment of advanced metastatic melanoma. Oncologist, 2000, 5(2), 144-151.
[http://dx.doi.org/10.1634/theoncologist.5-2-144] [PMID: 10794805]
[18]
Hwu, W.J. New approaches in the treatment of metastatic melanoma: Thalidomide and temozolomide. Oncology (Williston Park), 2000, 14(12)(Suppl. 13), 25-28.
[PMID: 11204670]
[19]
Soape, M.P.; Verma, R.; Payne, J.D.; Wachtel, M.; Hardwicke, F.; Cobos, E. Treatment of Hepatic epithelioid hemangioendothelioma: finding uses for thalidomide in a new era of medicine. Case Rep. Gastrointest. Med., 2015, 2015326795
[20]
Eisen, T.; Boshoff, C.; Mak, I.; Sapunar, F.; Vaughan, M.M.; Pyle, L.; Johnston, S.R.D.; Ahern, R.; Smith, I.E.; Gore, M.E. Continuous low dose Thalidomide: A phase II study in advanced melanoma, renal cell, ovarian and breast cancer. Br. J. Cancer, 2000, 82(4), 812-817.
[http://dx.doi.org/10.1054/bjoc.1999.1004] [PMID: 10732751]
[21]
Hwang, C.; Heath, E.I. Angiogenesis inhibitors in the treatment of prostate cancer. J. Hematol. Oncol., 2010, 3(26), 26.
[http://dx.doi.org/10.1186/1756-8722-3-26] [PMID: 20678204]
[22]
Keifer, J.A.; Guttridge, D.C.; Ashburner, B.P.; Baldwin, A.S. Jr Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity. J. Biol. Chem., 2001, 276(25), 22382-22387.
[http://dx.doi.org/10.1074/jbc.M100938200] [PMID: 11297551]
[23]
Gasic, G.J.; Gasic, T.B.; Murphy, S. Anti-metastatic effect of aspirin. Lancet, 1972, 2(7783), 932-933.
[http://dx.doi.org/10.1016/S0140-6736(72)92581-0] [PMID: 4116642]
[24]
Rothwell, P.M.; Fowkes, F.G.; Belch, J.F.; Ogawa, H.; Warlow, C.P.; Meade, T.W. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet, 2011, 377(9759), 31-41.
[http://dx.doi.org/10.1016/S0140-6736(10)62110-1] [PMID: 21144578]
[25]
Din, F.V.; Theodoratou, E.; Farrington, S.M.; Tenesa, A.; Barnetson, R.A.; Cetnarskyj, R.; Stark, L.; Porteous, M.E.; Campbell, H.; Dunlop, M.G. Effect of aspirin and NSAIDs on risk and survival from colorectal cancer. Gut, 2010, 59(12), 1670-1679.
[http://dx.doi.org/10.1136/gut.2009.203000] [PMID: 20844293]
[26]
Turini, M.E.; DuBois, R.N. Cyclooxygenase-2: A therapeutic target. Annu. Rev. Med., 2002, 53, 35-57.
[http://dx.doi.org/10.1146/annurev.med.53.082901.103952] [PMID: 11818462]
[27]
Sobolewski, C.; Cerella, C.; Dicato, M.; Ghibelli, L.; Diederich, M. The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies. Int. J. Cell Biol., 2010, 2010215158
[http://dx.doi.org/10.1155/2010/215158]
[28]
Lanas, A. Clinical experience with cyclooxygenase-2 inhibitors. Rheumatology (Oxford), 2002, 41(Suppl. 1), 16-22.
[http://dx.doi.org/10.1093/rheumatology/41.S1.16] [PMID: 12173276]
[29]
FitzGerald, G.A.; Patrono, C. The coxibs, selective inhibitors of cyclooxygenase-2. N. Engl. J. Med., 2001, 345(6), 433-442.
[http://dx.doi.org/10.1056/NEJM200108093450607] [PMID: 11496855]
[30]
Jendrossek, V. Targeting apoptosis pathways by celecoxib in cancer. Cancer Lett., 2013, 332(2), 313-324.
[http://dx.doi.org/10.1016/j.canlet.2011.01.012] [PMID: 21345578]
[31]
Steinbach, G.; Lynch, P.M.; Phillips, R.K.; Wallace, M.H.; Hawk, E.; Gordon, G.B.; Wakabayashi, N.; Saunders, B.; Shen, Y.; Fujimura, T.; Su, L.K.; Levin, B.; Godio, L.; Patterson, S.; Rodriguez-Bigas, M.A.; Jester, S.L.; King, K.L.; Schumacher, M.; Abbruzzese, J.; DuBois, R.N.; Hittelman, W.N.; Zimmerman, S.; Sherman, J.W.; Kelloff, G. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N. Engl. J. Med., 2000, 342(26), 1946-1952.
[http://dx.doi.org/10.1056/NEJM200006293422603] [PMID: 10874062]
[32]
Schönthal, A.H. Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy. Br. J. Cancer, 2007, 97(11), 1465-1468.
[http://dx.doi.org/10.1038/sj.bjc.6604049] [PMID: 17955049]
[33]
Harris, R.E. Cyclooxygenase-2 (cox-2) blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung. Inflammopharmacology, 2009, 17(2), 55-67.
[http://dx.doi.org/10.1007/s10787-009-8049-8] [PMID: 19340409]
[34]
Friedman, G.D.; Ury, H.K. Initial screening for carcinogenicity of commonly used drugs. J. Natl. Cancer Inst., 1980, 65(4), 723-733.
[http://dx.doi.org/10.1093/jnci/65.4.723] [PMID: 6932525]
[35]
Harris, R.E.; Beebe-Donk, J.; Alshafie, G.A. Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2) inhibitors. BMC Cancer, 2006, 6, 27.
[http://dx.doi.org/10.1186/1471-2407-6-27] [PMID: 16445867]
[36]
Algra, A.M.; Rothwell, P.M. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol., 2012, 13(5), 518-527.
[http://dx.doi.org/10.1016/S1470-2045(12)70112-2] [PMID: 22440112]
[37]
Gong, L.; Thorn, C.F.; Bertagnolli, M.M.; Grosser, T.; Altman, R.B.; Klein, T.E. Celecoxib pathways: Pharmacokinetics and pharmacodynamics. Pharmacogenet. Genomics, 2012, 22(4), 310-318.
[http://dx.doi.org/10.1097/FPC.0b013e32834f94cb] [PMID: 22336956]
[38]
Gupta, S.C.; Sung, B.; Prasad, S.; Webb, L.J.; Aggarwal, B.B. Cancer drug discovery by repurposing: Teaching new tricks to old dogs. Trends Pharmacol. Sci., 2013, 34(9), 508-517.
[http://dx.doi.org/10.1016/j.tips.2013.06.005] [PMID: 23928289]
[39]
Regulski, M.; Regulska, K.; Prukała, W.; Piotrowska, H.; Stanisz, B.; Murias, M. COX-2 inhibitors: A novel strategy in the management of breast cancer. Drug Discov. Today, 2016, 21(4), 598-615.
[http://dx.doi.org/10.1016/j.drudis.2015.12.003] [PMID: 26723915]
[40]
Falandry, C.; Debled, M.; Bachelot, T.; Delozier, T.; Crétin, J.; Romestaing, P.; Mille, D.; You, B.; Mauriac, L.; Pujade-Lauraine, E.; Freyer, G. Celecoxib and exemestane versus placebo and exemestane in postmenopausal metastatic breast cancer patients: A double-blind phase III GINECO study. Breast Cancer Res. Treat., 2009, 116(3), 501-508.
[http://dx.doi.org/10.1007/s10549-008-0229-5] [PMID: 19020973]
[41]
Chateauvieux, S.; Morceau, F.; Dicato, M.; Marc Diederich, M. Molecular and therapeutic potential and toxicity of valproic acid. J. Biomed. Biotechnol., 2010.479364
[http://dx.doi.org/10.1155/2010/479364]
[42]
Kostrouchová, M.; Kostrouch, Z.; Kostrouchová, M. Valproic acid, a molecular lead to multiple regulatory pathways. Folia Biol. (Praha), 2007, 53(2), 37-49.
[PMID: 17448293]
[43]
Blaheta, R.A.; Michaelis, M.; Driever, P.H.; Cinatl, J., Jr Evolving anticancer drug valproic acid: Insights into the mechanism and clinical studies. Med. Res. Rev., 2005, 25(4), 383-397.
[http://dx.doi.org/10.1002/med.20027] [PMID: 15637697]
[44]
Raffoux, E.; Chaibi, P.; Dombret, H.; Degos, L. Valproic acid and all-trans retinoic acid for the treatment of elderly patients with acute myeloid leukemia. Haematologica, 2005, 90(7), 986-988.
[PMID: 15996941]
[45]
Michaelis, M.; Doerr, H.W.; Cinatl, J., Jr Valproic acid as anti-cancer drug. Curr. Pharm. Des., 2007, 13(33), 3378-3393.
[http://dx.doi.org/10.2174/138161207782360528] [PMID: 18045192]
[46]
Abdul, M.; Hoosein, N. Inhibition by anticonvulsants of prostate-specific antigen and interleukin-6 secretion by human prostate cancer cells. Anticancer Res., 2001, 21(3B), 2045-2048.
[PMID: 11497296]
[47]
Krämer, O.H.; Baus, D.; Knauer, S.K.; Stein, S.; Jäger, E.; Stauber, R.H.; Grez, M.; Pfitzner, E.; Heinzel, T. Acetylation of Stat1 modulates NF-kappaB activity. Genes Dev., 2006, 20(4), 473-485.
[http://dx.doi.org/10.1101/gad.364306] [PMID: 16481475]
[48]
Ziauddin, M.F.; Yeow, W-S.; Maxhimer, J.B.; Baras, A.; Chua, A.; Reddy, R.M.; Tsai, W.; Cole, G.W., Jr; Schrump, D.S.; Nguyen, D.M. Valproic acid, an antiepileptic drug with histone deacetylase inhibitory activity, potentiates the cytotoxic effect of Apo2L/TRAIL on cultured thoracic cancer cells through mitochondria-dependent caspase activation. Neoplasia, 2006, 8(6), 446-457.
[http://dx.doi.org/10.1593/neo.05823] [PMID: 16820090]
[49]
Venkataramani, V.; Rossner, C.; Iffland, L.; Schweyer, S.; Tamboli, I.Y.; Walter, J.; Wirths, O.; Bayer, T.A. Histone deacetylase inhibitor valproic acid inhibits cancer cell proliferation via down-regulation of the alzheimer amyloid precursor protein. J. Biol. Chem., 2010, 285(14), 10678-10689.
[http://dx.doi.org/10.1074/jbc.M109.057836] [PMID: 20145244]
[50]
Nelson, M.; Yang, M.; Dowle, A.A.; Thomas, J.R.; Brackenbury, W.J. The sodium channel-blocking antiepileptic drug phenytoin inhibits breast tumour growth and metastasis. Mol. Cancer, 2015, 14(13), 13.
[http://dx.doi.org/10.1186/s12943-014-0277-x] [PMID: 25623198]
[51]
Pellegrino, M.; Rizza, P.; Nigro, A.; Ceraldi, R.; Ricci, E.; Perrotta, I.; Aquila, S.; Lanzino, M.; Andò, S.; Morelli, C.; Sisci, D. FoxO3a mediates the inhibitory effects of the antiepileptic drug lamotrigine on breast cancer growth. Mol. Cancer Res., 2018, 16(6), 923-934.
[http://dx.doi.org/10.1158/1541-7786.MCR-17-0662] [PMID: 29523760]
[52]
Papanagnou, P.; Stivarou, T.; Papageorgiou, I.; Papadopoulos, G.E.; Pappas, A. Marketed drugs used for the management of hypercholesterolemia as anticancer armament. OncoTargets Ther., 2017, 10, 4393-4411.
[http://dx.doi.org/10.2147/OTT.S140483] [PMID: 28932124]
[53]
Burke, L.P.; Kukoly, C.A. Statins induce lethal effects in acute myeloblastic leukemia cells within 72 hours. Leuk. Lymphoma, 2008, 49(2), 322-330.
[http://dx.doi.org/10.1080/10428190701760011] [PMID: 18231920]
[54]
Chae, Y.K.; Yousaf, M.; Malecek, M-K.; Carneiro, B.; Chandra, S.; Kaplan, J.; Kalyan, J.; Sassano, A.; Platanias, L.C.; Giles, F. 2015.http://www.discoverymedicine.com
[55]
Crosbie, J.; Magnussen, M.; Dornbier, R.; Iannone, A.; Steele, T.A. Statins inhibit proliferation and cytotoxicity of a human leukemic natural killer cell line. Biomark. Res., 2013, 1(1), 33.
[http://dx.doi.org/10.1186/2050-7771-1-33] [PMID: 24359683]
[56]
Ahn, K.S.; Sethi, G.; Aggarwal, B.B. Simvastatin potentiates TNF-alpha-induced apoptosis through the down-regulation of NF-kappaB-dependent antiapoptotic gene products: role of IkappaBalpha kinase and TGF-beta-activated kinase-1. J. Immunol., 2007, 178(4), 2507-2516.
[http://dx.doi.org/10.4049/jimmunol.178.4.2507] [PMID: 17277159]
[57]
Broughton, T.; Sington, J.; Beales, I.L.P. Statin use is associated with a reduced incidence of colorectal cancer: a colonoscopy-controlled case-control study. BMC Gastroenterol., 2012, 12, 36.
[http://dx.doi.org/10.1186/1471-230X-12-36] [PMID: 22530742]
[58]
Coogan, P.F.; Smith, J.; Rosenberg, L. Statin use and risk of colorectal cancer. J. Natl. Cancer Inst., 2007, 99(1), 32-40.
[http://dx.doi.org/10.1093/jnci/djk003] [PMID: 17202111]
[59]
Shadman, M.; Mawad, R.; Dean, C.; Chen, T.L.; Shannon-Dorcy, K.; Sandhu, V.; Hendrie, P.C.; Scott, B.L.; Walter, R.B.; Becker, P.S.; Pagel, J.M.; Estey, E.H. Idarubicin, cytarabine, and pravastatin as induction therapy for untreated acute myeloid leukemia and high-risk myelodysplastic syndrome. Am. J. Hematol., 2015, 90(6), 483-486.
[http://dx.doi.org/10.1002/ajh.23981] [PMID: 25689471]
[60]
Pradelli, D.; Soranna, D.; Zambon, A.; Catapano, A.; Mancia, G.; La Vecchia, C.; Corrao, G. Statins use and the risk of all and subtype hematological malignancies: A meta-analysis of observational studies. Cancer Med., 2015, 4(5), 770-780.
[http://dx.doi.org/10.1002/cam4.411] [PMID: 25809667]
[61]
Altwairgi, A.K. Statins are potential anticancerous agents (review). Oncol. Rep., 2015, 33(3), 1019-1039.
[http://dx.doi.org/10.3892/or.2015.3741] [PMID: 25607255]
[62]
Kalender, A.; Selvaraj, A.; Kim, S.Y.; Gulati, P.; Brûlé, S.; Viollet, B.; Kemp, B.E.; Bardeesy, N.; Dennis, P.; Schlager, J.J.; Marette, A.; Kozma, S.C.; Thomas, G. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab., 2010, 11(5), 390-401.
[http://dx.doi.org/10.1016/j.cmet.2010.03.014] [PMID: 20444419]
[63]
Kasznicki, J.; Sliwinska, A.; Drzewoski, J. Metformin in cancer prevention and therapy. Ann. Transl. Med., 2014, 2(6), 57.
[PMID: 25333032]
[64]
Heckman-Stoddard, B.M.; DeCensi, A.; Sahasrabuddhe, V.V.; Ford, L.G. Repurposing metformin for the prevention of cancer and cancer recurrence. Diabetologia, 2017, 60(9), 1639-1647.
[http://dx.doi.org/10.1007/s00125-017-4372-6] [PMID: 28776080]
[65]
Bo, S.; Benso, A.; Durazzo, M.; Ghigo, E. Metformin blocks progression of obesity-activated thyroid cancer in a mouse model. J. Endocrinol. Invest., 2012, 35(2), 231-235.
[http://dx.doi.org/10.1007/BF03345423] [PMID: 22490993]
[66]
Bodmer, M.; Meier, C.; Krähenbühl, S.; Jick, S.S.; Meier, C.R. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care, 2010, 33(6), 1304-1308.
[http://dx.doi.org/10.2337/dc09-1791] [PMID: 20299480]
[67]
Jiralerspong, S.; Palla, S.L.; Giordano, S.H.; Meric-Bernstam, F.; Liedtke, C.; Barnett, C.M.; Hsu, L.; Hung, M.C.; Hortobagyi, G.N.; Gonzalez-Angulo, A.M. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J. Clin. Oncol., 2009, 27(20), 3297-3302.
[http://dx.doi.org/10.1200/JCO.2009.19.6410] [PMID: 19487376]
[68]
Campagnoli, C.; Pasanisi, P.; Abbà, C.; Ambroggio, S.; Biglia, N.; Brucato, T.; Colombero, R.; Danese, S.; Donadio, M.; Venturelli, E.; Zito, G.; Berrino, F. Effect of different doses of metformin on serum testosterone and insulin in non-diabetic women with breast cancer: a randomized study. Clin. Breast Cancer, 2012, 12(3), 175-182.
[http://dx.doi.org/10.1016/j.clbc.2012.03.004] [PMID: 22607767]
[69]
Hosono, K.; Endo, H.; Takahashi, H.; Sugiyama, M.; Sakai, E.; Uchiyama, T.; Suzuki, K.; Iida, H.; Sakamoto, Y.; Yoneda, K.; Koide, T.; Tokoro, C.; Abe, Y.; Inamori, M.; Nakagama, H.; Nakajima, A. Metformin suppresses colorectal aberrant crypt foci in a short-term clinical trial. Cancer Prev. Res. (Phila.), 2010, 3(9), 1077-1083.
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0186] [PMID: 20810669]
[70]
Zhou, X-L.; Xue, W-H.; Ding, X-F.; Li, L-F.; Dou, M-M.; Zhang, W-J.; Lv, Z.; Fan, Z-R.; Zhao, J.; Wang, L-X. Association between metformin and the risk of gastric cancer in patients with type 2 diabetes mellitus: A meta-analysis of cohort studies. Oncotarget, 2017, 8(33), 55622-55631.
[http://dx.doi.org/10.18632/oncotarget.16973] [PMID: 28903449]
[71]
Tseng, C-H. Metformin reduces gastric cancer risk in patients with type 2 diabetes mellitus. Aging (Albany NY), 2016, 8(8), 1636-1649.
[http://dx.doi.org/10.18632/aging.101019] [PMID: 27587088]
[72]
Li, P.; Zhang, C.; Gao, P.; Chen, X.; Ma, B.; Yu, D.; Song, Y.; Wang, Z. Metformin use and its effect on gastric cancer in patients with type 2 diabetes: A systematic review of observational studies. Oncol. Lett., 2018, 15(1), 1191-1199.
[PMID: 29391902]
[73]
Park, J.; Kim, W.G.; Zhao, L.; Enomoto, K.; Willingham, M.; Cheng, S.Y. Metformin blocks progression of obesity-activated thyroid cancer in a mouse model. Oncotarget, 2016, 7(23), 34832-34844.
[http://dx.doi.org/10.18632/oncotarget.8989] [PMID: 27145454]
[74]
Quinn, B.J.; Kitagawa, H.; Memmott, R.M.; Gills, J.J.; Dennis, P.A. Repositioning metformin for cancer prevention and treatment. Trends Endocrinol. Metab., 2013, 24(9), 469-480.
[http://dx.doi.org/10.1016/j.tem.2013.05.004] [PMID: 23773243]
[75]
Higginbotham, S.; Wong, W.R.; Linington, R.G.; Spadafora, C.; Iturrado, L.; Arnold, A.E. Sloth hair as a novel source of fungi with potent anti-parasitic, anti-cancer and anti-bacterial bioactivity. PLoS One, 2014, 9(1)e84549
[http://dx.doi.org/10.1371/journal.pone.0084549] [PMID: 24454729]
[76]
Johnston, W.T.; Mutalima, N.; Sun, D.; Emmanuel, B.; Bhatia, K.; Aka, P.; Wu, X.; Borgstein, E.; Liomba, G.N.; Kamiza, S.; Mkandawire, N.; Batumba, M.; Carpenter, L.M.; Jaffe, H.; Molyneux, E.M.; Goedert, J.J.; Soppet, D.; Newton, R.; Mbulaiteye, S.M. Relationship between Plasmodium falciparum malaria prevalence, genetic diversity and endemic Burkitt lymphoma in Malawi. Sci. Rep., 2014, 4, 3741.
[http://dx.doi.org/10.1038/srep03741] [PMID: 24434689]
[77]
Khan, K.H. DNA vaccines: Roles against diseases. Germs, 2013, 3(1), 26-35.
[http://dx.doi.org/10.11599/germs.2013.1034] [PMID: 24432284]
[78]
Fedosov, D.A.; Dao, M.; Karniadakis, G.E.; Suresh, S. Computational biorheology of human blood flow in health and disease. Ann. Biomed. Eng., 2014, 42(2), 368-387.
[http://dx.doi.org/10.1007/s10439-013-0922-3] [PMID: 24419829]
[79]
Hooft van Huijsduijnen, R.; Guy, R.K.; Chibale, K.; Haynes, R.K.; Peitz, I.; Kelter, G.; Phillips, M.A.; Vennerstrom, J.L.; Yuthavong, Y.; Wells, T.N. Anticancer properties of distinct antimalarial drug classes. PLoS One, 2013, 8(12)e82962
[http://dx.doi.org/10.1371/journal.pone.0082962] [PMID: 24391728]
[80]
Keum, K.-C.; Yoo, N.-C.; Yoo, W.-M.; Chang, K.K.; Choon, Y.N.; Min, Y.W. Anticancer composition composed of anticancer and anti-malarial drug. WO, 2002.
[81]
Liu, F.; Shang, Y.; Chen, S-Z. Chloroquine potentiates the anti-cancer effect of lidamycin on non-small cell lung cancer cells in vitro. Acta Pharmacol. Sin., 2014, 35(5), 645-652.
[http://dx.doi.org/10.1038/aps.2014.3] [PMID: 24727941]
[82]
Kamal, A.; Aziz, A.; Shouman, S.; El-Demerdash, E.; Elgendy, M.; Abdel-Naim, A.B. Chloroquine as a promising adjuvant chemothreaphy together with sunitinib. Sci. Proc, 2014, 1e384
[83]
Ganguli, A.; Choudhury, D.; Datta, S.; Bhattacharya, S.; Chakrabarti, G. Inhibition of autophagy by chloroquine potentiates synergistically anti-cancer property of artemisinin by promoting ROS dependent apoptosis. Biochimie, 2014, 107(Pt B), 338-349.
[http://dx.doi.org/ 10.1016/j.biochi.2014.10.001] [PMID: 25308836]
[84]
Soo, G.W.; Law, J.H.; Kan, E.; Tan, S.Y.; Lim, W.Y.; Chay, G.; Bukhari, N.I.; Segarra, I. Differential effects of ketoconazole and primaquine on the pharmacokinetics and tissue distribution of imatinib in mice. Anticancer Drugs, 2010, 21(7), 695-703.
[PMID: 20629201]
[85]
Wong, Y.K.; Xu, C.; Kalesh, K.A.; He, Y.; Lin, Q.; Wong, W.S.F.; Shen, H.M.; Wang, J. Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action. Med. Res. Rev., 2017, 37(6), 1492-1517.
[http://dx.doi.org/10.1002/med.21446] [PMID: 28643446]
[86]
Efferth, T. From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy. Semin. Cancer Biol., 2017, 46, 65-83.
[http://dx.doi.org/10.1016/j.semcancer.2017.02.009] [PMID: 28254675]
[87]
Olliaro, P.L.; Haynes, R.K.; Meunier, B.; Yuthavong, Y. Possible modes of action of the artemisinin-type compounds. Trends Parasitol., 2001, 17(3), 122-126.
[http://dx.doi.org/10.1016/S1471-4922(00)01838-9] [PMID: 11286794]
[88]
Zhang, S.; Gerhard, G.S. Heme mediates cytotoxicity from artemisinin and serves as a general anti-proliferation target. PLoS One, 2009, 4(10)e7472
[http://dx.doi.org/10.1371/journal.pone.0007472] [PMID: 19862332]
[89]
Hamacher-Brady, A.; Stein, H.A.; Turschner, S.; Toegel, I.; Mora, R.; Jennewein, N.; Efferth, T.; Eils, R.; Brady, N.R. Artesunate activates mitochondrial apoptosis in breast cancer cells via iron-catalyzed lysosomal reactive oxygen species production. J. Biol. Chem., 2011, 286(8), 6587-6601.
[http://dx.doi.org/10.1074/jbc.M110.210047] [PMID: 21149439]
[90]
Das, A.K. Anticancer effect of antimalarial artemisinin compounds. Ann. Med. Health Sci. Res., 2015, 5(2), 93-102.
[http://dx.doi.org/10.4103/2141-9248.153609] [PMID: 25861527]
[91]
Mercer, A.E.; Maggs, J.L.; Sun, X.M.; Cohen, G.M.; Chadwick, J.; O’Neill, P.M.; Park, B.K. Evidence for the involvement of carbon-centered radicals in the induction of apoptotic cell death by artemisinin compounds. J. Biol. Chem., 2007, 282(13), 9372-9382.
[http://dx.doi.org/10.1074/jbc.M610375200] [PMID: 17227762]
[92]
Mercer, A.E.; Copple, I.M.; Maggs, J.L.; O’Neill, P.M.; Park, B.K. The role of heme and the mitochondrion in the chemical and molecular mechanisms of mammalian cell death induced by the artemisinin antimalarials. J. Biol. Chem., 2011, 286(2), 987-996.
[http://dx.doi.org/10.1074/jbc.M110.144188] [PMID: 21059641]
[93]
Bostwick, D.G.; Alexander, E.E.; Singh, R.; Shan, A.; Qian, J.; Santella, R.M.; Oberley, L.W.; Yan, T.; Zhong, W.; Jiang, X.; Oberley, T.D. Antioxidant enzyme expression and reactive oxygen species damage in prostatic intraepithelial neoplasia and cancer. Cancer, 2000, 89(1), 123-134.
[http://dx.doi.org/10.1002/1097-0142(20000701)89:1<123:AID-CNCR17>3.0.CO;2-9] [PMID: 10897009]
[94]
Lu, J.J.; Chen, S.M.; Zhang, X.W.; Ding, J.; Meng, L.H. The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells. Invest. New Drugs, 2011, 29(6), 1276-1283.
[http://dx.doi.org/10.1007/s10637-010-9481-8] [PMID: 20607588]
[95]
Anfosso, L.; Efferth, T.; Albini, A.; Pfeffer, U. Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins. Pharmacogenomics J., 2006, 6(4), 269-278.
[http://dx.doi.org/10.1038/sj.tpj.6500371] [PMID: 16432535]
[96]
Nqoro, X.; Tobeka, N.; Aderibigbe, B.A. Quinoline-based hybrid compounds with antimalarial activity. Molecules, 2017, 22(12), 2268-2290.
[http://dx.doi.org/10.3390/molecules22122268] [PMID: 29257067]
[97]
Lu, Y.Y.; Chen, T.S.; Qu, J.L.; Pan, W.L.; Sun, L.; Wei, X.B. Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells. J. Biomed. Sci., 2009, 16, 16.
[http://dx.doi.org/10.1186/1423-0127-16-16] [PMID: 19272183]
[98]
Zhou, C.; Pan, W.; Wang, X.P.; Chen, T.S. Artesunate induces apoptosis via a Bak-mediated caspase-independent intrinsic pathway in human lung adenocarcinoma cells. J. Cell. Physiol., 2012, 227(12), 3778-3786.
[http://dx.doi.org/10.1002/jcp.24086] [PMID: 22378505]
[99]
Efferth, T.; Sauerbrey, A.; Olbrich, A.; Gebhart, E.; Rauch, P.; Weber, H.O.; Hengstler, J.G.; Halatsch, M.E.; Volm, M.; Tew, K.D.; Ross, D.D.; Funk, J.O. Molecular modes of action of artesunate in tumor cell lines. Mol. Pharmacol., 2003, 64(2), 382-394.
[http://dx.doi.org/10.1124/mol.64.2.382] [PMID: 12869643]
[100]
Augustin, Y.; Krishna, S.; Kumar, D.; Pantziarka, P. The wisdom of crowds and the repurposing of artesunate as an anticancer drug. Ecancer. Ecancermedicalscience, 2015, 9ed50
[http://dx.doi.org/10.3332/ecancer.2015.ed50.]
[101]
Džimbeg, G.; Zorc, B.; Kralj, M.; Ester, K.; Pavelić, K.; Andrei, G.; Snoeck, R.; Balzarini, J.; De Clercq, E.; Mintas, M. The novel primaquine derivatives of N-alkyl, cycloalkyl or aryl urea: Synthesis, cytostatic and antiviral activity evaluations. Eur. J. Med. Chem., 2008, 43(6), 1180-1187.
[http://dx.doi.org/10.1016/j.ejmech.2007.09.001] [PMID: 17961851]
[102]
Simunović, M.; Perković, I.; Zorc, B.; Ester, K.; Kralj, M.; Hadjipavlou-Litina, D.; Pontiki, E. Urea and carbamate derivatives of primaquine: synthesis, cytostatic and antioxidant activities. Bioorg. Med. Chem., 2009, 17(15), 5605-5613.
[http://dx.doi.org/10.1016/j.bmc.2009.06.030] [PMID: 19581098]
[103]
Perković, I.; Tršinar, S.; Žanetić, J.; Kralj, M.; Martin-Kleiner, I.; Balzarini, J.; Hadjipavlou-Litina, D.A.M.; Katsori, B.; Zorc, B. Novel 1-acyl-4-substituted semicarbazide derivativesof primaquine-synthesis, cytostatic, antiviral and antioxidative studies. J. Enzyme Inhib. Med. Chem., 2013, 28, 601-610.
[http://dx.doi.org/10.3109/14756366.2012.663366] [PMID: 22380782]
[104]
Pavić, K.; Perković, I.; Cindrić, M.; Pranjić, M.; Martin-Kleiner, I.; Kralj, M.; Schols, D.; Hadjipavlou-Litina, D.; Katsori, A-M.; Zorc, B. Synthesis, biological evaluation, and quantitative structure-activity relationship analysis of new schiff bases of hydroxysemicarbazide as potential antitumor agents. Eur. J. Med. Chem., 2014, 86, 502-514.
[PMID: 25203780]
[105]
Perković, I.; Antunović, M.; Marijanović, I.; Pavić, K.; Ester, K.; Kralj, M.; Vlainić, J.; Kosalec, I.; Schols, D.; Hadjipavlou-Litina, D.; Pontiki, E.; Zorc, B. Novel urea and bis-urea primaquine derivatives with hydroxyphenyl or halogenphenyl substituents: Synthesis and biological evaluation. Eur. J. Med. Chem., 2016, 124, 622-636.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.021] [PMID: 27614409]
[106]
Pavić, K.; Perković, I.; Gilja, P.; Kozlina, F.; Ester, K.; Kralj, M.; Schols, D.; Hadjipavlou-Litina, D.; Pontiki, E.; Zorc, B. Design, synthesis and biological evaluation of novel primaquine-cinnamic acid conjugates of the amide and acylsemicarbazide type. Molecules, 2016, 21(12), 1629-1653.
[http://dx.doi.org/10.3390/molecules21121629] [PMID: 27916811]
[107]
Pavić, K.; Perković, I.; Pospíšilová, Š.; Machado, M.; Fontinha, D.; Prudêncio, M.; Jampilek, J.; Coffey, A.; Endersen, L.; Rimac, H.; Zorc, B. Primaquine hybrids as promising antimycobacterial and antimalarial agents. Eur. J. Med. Chem., 2018, 143, 769-779.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.083] [PMID: 29220797]
[108]
Xu, X.; Wang, J.; Han, K.; Li, S.; Xu, F.; Yang, Y. Antimalarial drug mefloquine inhibits nuclear factor kappa B signaling and induces apoptosis in colorectal cancer cells. Cancer Sci., 2018, 109(4), 1220-1229.
[http://dx.doi.org/10.1111/cas.13540] [PMID: 29453896]
[109]
Verbaanderd, C.; Maes, H.; Schaaf, M.B.; Sukhatme, V.P.; Pantziarka, P.; Sukhatme, V.; Agostinis, P.; Bouche, G. Repurposing Drugs in Oncology (ReDO)-chloroquine and hydroxychloroquine as anti-cancer agents. Ecancermedicalscience, 2017, 11, 781.
[http://dx.doi.org/10.3332/ecancer.2017.781] [PMID: 29225688]
[110]
Shaimerdenova, M.; Karapina, O.; Mektepbayeva, D.; Alibek, K.; Akilbekova, D. The effects of antiviral treatment on breast cancer cell line. Infect. Agent. Cancer, 2017, 12, 18.
[http://dx.doi.org/10.1186/s13027-017-0128-7] [PMID: 28344640]
[111]
Monini, P.; Sgadari, C.; Toschi, E.; Barillari, G.; Ensoli, B. Antitumour effects of antiretroviral therapy. Nat. Rev. Cancer, 2004, 4(11), 861-875.
[http://dx.doi.org/10.1038/nrc1479] [PMID: 15516959]
[112]
Mitsuya, H.; Weinhold, K.J.; Furman, P.A.; St Clair, M.H.; Lehrman, S.N.; Gallo, R.C.; Bolognesi, D.; Barry, D.W.; Broder, S. 3′-Azido-3′-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc. Natl. Acad. Sci. USA, 1985, 82(20), 7096-7100.
[http://dx.doi.org/10.1073/pnas.82.20.7096] [PMID: 2413459]
[113]
Namba, T.; Kodama, R.; Moritomo, S.; Hoshino, T.; Mizushima, T. Zidovudine, an anti-viral drug, resensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine by inhibition of the Akt-GSK3β-Snail pathway. Cell Death Dis., 2015, 6e1795
[http://dx.doi.org/10.1038/cddis.2015.172] [PMID: 26111057]
[114]
Aschacher, T.; Sampl, S.; Käser, L.; Bernhard, D.; Spittler, A.; Holzmann, K.; Bergmann, M. The combined use of known antiviral reverse transcriptase inhibitors AZT and DDI induce anticancer effects at low concentrations. Neoplasia, 2012, 14(1), 44-53.
[http://dx.doi.org/10.1593/neo.11426] [PMID: 22355273]
[115]
Chong, C.R.; Xu, J.; Lu, J.; Bhat, S.; Sullivan, D.J., Jr; Liu, J.O. Inhibition of angiogenesis by the antifungal drug itraconazole. ACS Chem. Biol., 2007, 2(4), 263-270.
[http://dx.doi.org/10.1021/cb600362d] [PMID: 17432820]
[116]
Pounds, R.; Leonard, S.; Dawson, C.; Kehoe, S. Repurposing itraconazole for the treatment of cancer. Oncol. Lett., 2017, 14(3), 2587-2597.
[http://dx.doi.org/10.3892/ol.2017.6569] [PMID: 28927025]
[117]
Pantziarka, P.; Sukhatme, V.; Bouche, G.; Meheus, L.; Sukhatme, V.P. Repurposing drugs in oncology (ReDO)-itraconazole as an anti-cancer agent. Ecancermedicalscience, 2015, 9, 521.
[http://dx.doi.org/10.3332/ecancer.2015.521] [PMID: 25932045]
[118]
Cha, H.J.; Byrom, M.; Mead, P.E.; Ellington, A.D.; Wallingford, J.B.; Marcotte, E.M. Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent. PLoS Biol., 2012, 10(8)e1001379
[http://dx.doi.org/10.1371/journal.pbio.1001379] [PMID: 22927795]
[119]
Seto, B. Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer. Clin. Transl. Med., 2012, 1(1), 29.
[http://dx.doi.org/10.1186/2001-1326-1-29] [PMID: 23369283]
[120]
Chen, B.; Wei, W.; Ma, L.; Yang, B.; Gill, R.M.; Chua, M.S.; Butte, A.J.; So, S. Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells in vitro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology, 2017, 152(8), 2022-2036.
[http://dx.doi.org/10.1053/j.gastro.2017.02.039] [PMID: 28284560]
[121]
Pantziarka, P.; Bouche, G.; Meheus, L.; Sukhatme, V.; Sukhatme, V.P. Repurposing drugs in oncology (ReDO)-mebendazole as an anti-cancer agent. Ecancermedicalscience, 2014, 8, 443.
[http://dx.doi.org/10.3332/ecancer.2014.485] [PMID: 25075217]
[122]
Polascik, T.J.; Mouraviev, V. Zoledronic acid in the management of metastatic bone disease. Ther. Clin. Risk Manag., 2008, 4(1), 261-268.
[http://dx.doi.org/10.2147/TCRM.S2707] [PMID: 18728715]
[123]
Ding, X. Drug screening: Drug repositioning needs a rethink. Nature, 2016, 535(7612), 355.
[http://dx.doi.org/10.1038/535355d] [PMID: 27443733]
[124]
Doudican, N.A.; Kumar, A.; Singh, N.K.; Nair, P.R.; Lala, D.A.; Basu, K.; Talawdekar, A.A.; Sultana, Z.; Tiwari, K.K.; Tyagi, A.; Abbasi, T.; Vali, S.; Vij, R.; Fiala, M.; King, J.; Perle, M.; Mazumder, A. Personalization of cancer treatment using predictive simulation. J. Transl. Med., 2015, 13, 43.
[http://dx.doi.org/10.1186/s12967-015-0399-y] [PMID: 25638213]
[125]
Cheng, F.; Hong, H.; Yang, S.; Wei, Y. Individualized network-based drug repositioning infrastructure for precision oncology in the panomics era. Brief. Bioinform., 2017, 18(4), 682-697.
[PMID: 27296652]
[126]
Hyman, D.M.; Taylor, B.S.; Baselga, J. Implementing genome-driven oncology. Cell, 2017, 168(4), 584-599.
[http://dx.doi.org/10.1016/j.cell.2016.12.015] [PMID: 28187282]
[127]
Rastegar-Mojarad, M.; Liu, H.; Nambisan, P. Using social media data to identify potential candidates for drug repurposing: A feasibility study. JMIR Res. Protoc., 2016, 5(2)e121
[http://dx.doi.org/10.2196/resprot.5621] [PMID: 27311964]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version346msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[18:24:55] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[18:24:55] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[18:24:55] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (105ms)time
  • Application (241ms)time
  • 1 x Application (69.68%)
    241ms
    1 x Booting (30.32%)
    105ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated171ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('316381173','',1,1740421495,1740421495) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740421495
      880μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('316381173','/article/91704',1,1740421495,1740421495)
      150μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) limit 1
      17.89msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316381173
      • 1: 316381173
      • 2: 316381173
      • 3: 316381173
      • 4: 316381173
      • 5: 316381173
      • 6: 316381173
      • 7: 316381173
      • 8: 316381173
      • 9: 316381173
      • 10: 316381173
      • 11: 316381173
      • 12: 316381173
      • 13: 316381173
      • 14: 316381173
      • 15: 316381173
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=91704
      750μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 25 limit 1
      880μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 25
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and sj.journal_id!=25 group by `j`.`nid`) as `aggregate_table`
      1.45msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and sj.journal_id!=25 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.2msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      3.52msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.93msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '91704'
      1.64msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 91704
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '91704'
      5.07msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 91704
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '91704' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      5.47msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 91704
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      310μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      470μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 25 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      30.56msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      49.49msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      31.35msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 91704 limit 1
      940μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 91704
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 91704 and content_type = 'article' order by status desc limit 1
      350μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 163766 limit 1
      240μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 163766
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      270μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CMC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      410μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CMC
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '91704' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      400μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '9419' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      370μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '2572' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      330μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316381173 and j.to_ip >=316381173 )) and ((j.from_date <= 1740421495 and j.to_date >= 1740421495 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2572) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316381173 and j.to_ip >=316381173 )) and ((j.from_date <= 1740421495 and j.to_date >= 1740421495 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2572) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316381173 and j.to_ip >=316381173 )) and ((j.from_date <= 1740421495 and j.to_date >= 1740421495 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2572)
      6.8msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316381173 and j.to_ip >=316381173 )) and ((j.from_date <= 1740421495 and j.to_date >= 1740421495 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9419) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316381173 and j.to_ip >=316381173 )) and ((j.from_date <= 1740421495 and j.to_date >= 1740421495 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9419) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316381173 and j.to_ip >=316381173 )) and ((j.from_date <= 1740421495 and j.to_date >= 1740421495 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9419)
      690μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316381173 and j.to_ip >=316381173 )) and ((j.from_date <= 1740421495 and j.to_date >= 1740421495 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 91704) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316381173 and j.to_ip >=316381173 )) and ((j.from_date <= 1740421495 and j.to_date >= 1740421495 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 91704) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316381173 and j.to_ip >=316381173 )) and ((j.from_date <= 1740421495 and j.to_date >= 1740421495 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 91704)
      640μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '5410' and is_uploaded = 1 and issue_id = 9419 order by cast(first_page as SIGNED) desc limit 1
      550μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 5410
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '5427' and is_uploaded = 1 and issue_id = 9419 order by cast(first_page as SIGNED) asc limit 1
      450μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 5427
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      220μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      240μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 91704 limit 1
      1.59msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 91704
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 25 and `b`.`banner_from_date` <= 1740421495 and `b`.`banner_to_date` >= 1740421495 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.17msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 25
      • 3: 1740421495
      • 4: 1740421495
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 25 and `b`.`banner_from_date` <= 1740421495 and `b`.`banner_to_date` >= 1740421495 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.15msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 25
      • 3: 1740421495
      • 4: 1740421495
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='3aef1bb47ae7e7b202b2022fbfff36ec'
      260μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
    App\Models\MultiLangArticle
    1MultiLangArticle.php#?
        _token
        wjjt1dnmaqQaXBqtkMTxM9ZW2Oj6Qb0GuiGYPPHe
        uc_cart_id
        3aef1bb47ae7e7b202b2022fbfff36ec
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/91704" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/91704
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Mon, 24 Feb 2025 18:24:55 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImhldDhSV09OZlV3UWhSVFBHN0FlYWc9PSIsInZhbHVlIjoiQnVrTVUxMnNkaXMyWFNwU284K1p5ajJTeVpjTlRadGFmQUFjUHl5NHZ4WWJkL3hnYzgrc1ZsZHJwbjVyQ0hMQU9OVzZzTkczMUZoQVNmUk5EMi9ROFU1NmJVWGRnbmRyMmpnU1RiTDBCdWY5SCtmaDRSc29IR0RGVmt4TG9vU1QiLCJtYWMiOiIzMTEzZGU2OWUxZDYzNWJlZDliYTBlZDY1M2M2ZGZhNmU4NzQ1MDQwYjEyMzFhNjlkNDhjNGRiMGFmZGFhNDgxIiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 06:24:55 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6ImhldDhSV09OZlV3UWhSVFBHN0FlYWc9PSIsInZhbHVlIjoiQnVrTVUxMnNkaXMyWFNwU284K1p5ajJTeVpjTlRadGFmQUFjUHl5NHZ4WWJkL3hnYzgrc1ZsZHJwbjVyQ0hMQU9OVzZzT" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkU2S2tJMUx5d2tOZmJZTmRmUTlpSXc9PSIsInZhbHVlIjoiQ014SnBNUHVWYkR6YS9QWk5IZGpWU2hUN1grcGkvYjNaMUlOVldobFJiVHBaVXZLa095WDlSdFpSMGhncW9hbElCOXZ6TTZxTVM1ZHNxZFNicmFYd0NkbnN5bnd2UXZKMWNzeHNUc1ZtSlpYZUNhVjlMeGxhbUFTRFg2ZkdlQWQiLCJtYWMiOiI3NjM2ZmI5ZDliOWE5ODk1M2M2OTVkMmVlZmU1NGVlMzcyZDAyOTcxY2YzMzhmMTY2NjM2Y2MwMjg0ZTYzOWZjIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IkU2S2tJMUx5d2tOZmJZTmRmUTlpSXc9PSIsInZhbHVlIjoiQ014SnBNUHVWYkR6YS9QWk5IZGpWU2hUN1grcGkvYjNaMUlOVldobFJiVHBaVXZLa095WDlSdFp" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImhldDhSV09OZlV3UWhSVFBHN0FlYWc9PSIsInZhbHVlIjoiQnVrTVUxMnNkaXMyWFNwU284K1p5ajJTeVpjTlRadGFmQUFjUHl5NHZ4WWJkL3hnYzgrc1ZsZHJwbjVyQ0hMQU9OVzZzTkczMUZoQVNmUk5EMi9ROFU1NmJVWGRnbmRyMmpnU1RiTDBCdWY5SCtmaDRSc29IR0RGVmt4TG9vU1QiLCJtYWMiOiIzMTEzZGU2OWUxZDYzNWJlZDliYTBlZDY1M2M2ZGZhNmU4NzQ1MDQwYjEyMzFhNjlkNDhjNGRiMGFmZGFhNDgxIiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 06:24:55 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6ImhldDhSV09OZlV3UWhSVFBHN0FlYWc9PSIsInZhbHVlIjoiQnVrTVUxMnNkaXMyWFNwU284K1p5ajJTeVpjTlRadGFmQUFjUHl5NHZ4WWJkL3hnYzgrc1ZsZHJwbjVyQ0hMQU9OVzZzT" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkU2S2tJMUx5d2tOZmJZTmRmUTlpSXc9PSIsInZhbHVlIjoiQ014SnBNUHVWYkR6YS9QWk5IZGpWU2hUN1grcGkvYjNaMUlOVldobFJiVHBaVXZLa095WDlSdFpSMGhncW9hbElCOXZ6TTZxTVM1ZHNxZFNicmFYd0NkbnN5bnd2UXZKMWNzeHNUc1ZtSlpYZUNhVjlMeGxhbUFTRFg2ZkdlQWQiLCJtYWMiOiI3NjM2ZmI5ZDliOWE5ODk1M2M2OTVkMmVlZmU1NGVlMzcyZDAyOTcxY2YzMzhmMTY2NjM2Y2MwMjg0ZTYzOWZjIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IkU2S2tJMUx5d2tOZmJZTmRmUTlpSXc9PSIsInZhbHVlIjoiQ014SnBNUHVWYkR6YS9QWk5IZGpWU2hUN1grcGkvYjNaMUlOVldobFJiVHBaVXZLa095WDlSdFp" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "wjjt1dnmaqQaXBqtkMTxM9ZW2Oj6Qb0GuiGYPPHe" "uc_cart_id" => "3aef1bb47ae7e7b202b2022fbfff36ec" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/91704" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-24 18:24:55GET/article/91704314362