CoChat
Sign Up
Cited by 5Endometrial and Cervical Cancer TreatmentsCancer, Lipids, and MetabolismOvarian cancer diagnosis and treatment

Potential Benefits of Adding Alendronate, Celecoxib, Itraconazole, Ramelteon, and Simvastatin to Endometrial Cancer Treatment: The EC5 Regimen

Open access
Kast, Richard E.·2025·Current Issues in Molecular Biology
DOI 10.3390/cimb47030153PMC PMC11941490
Open this paper in CoChat — free account

Abstract

Metastatic endometrial cancer continues to be a common cause of death as of 2024, even after maximal use of all currently available standard treatments. To address this problem of metastatic cancer generally in 2025, the drug repurposing movement within oncology identifies medicines in common general medical use that have clinical or preclinical experimental data indicating that they interfere with or inhibit a specific growth driving element identified in a given cancer. The drug repurposing movement within oncology also uses data from large scale in vitro screens of thousands of drugs, looking for simple empirical growth inhibition in a given cancer type. This paper outlines the data showing that five drugs from general medical practice meet these evidence criteria for inhibition of endometrial cancer growth, the EC5 regimen. The EC5 regimen uses the osteoporosis treatment drug, alendronate; the analgesic drug, celecoxib; the antifungal drug, itraconazole; the sleep aid, ramelteon; and the cholesterol lowering drug, simvastatin. Side effects seen with these drugs are usually minimal and easily tolerated by patients.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/cimb47030153

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 303

  1. [1]Kast R.E. IPIAD—An augmentation regimen added to standard treatment of pancreatic ductal adenocarcinoma using already-marketed repurposed drugs irbesartan, pyrimethamine, itraconazole, azithromycin, and dapsone Oncoscience 2024 11 15 31 10.18632/oncoscience.594 38524376 PMC10959018 · DOI · Paper page
  2. [2]Kast R.E. The OSR9 Regimen: A New Augmentation Strategy for Osteosarcoma Treatment Using Nine Older Drugs from General Medicine to Inhibit Growth Drive Int. J. Mol. Sci. 2023 24 15474 10.3390/ijms242015474 37895152 PMC10607234 · DOI
  3. [3]Kast R.E. Alfieri A. Assi H.I. Burns T.C. Elyamany A.M. Gonzalez-Cao M. Karpel-Massler G. Marosi C. Salacz M.E. Sardi I. MDACT: A New Principle of Adjunctive Cancer Treatment Using Combinations of Multiple Repurposed Drugs, with an Example Regimen Cancers 2022 14 2563 10.3390/cancers14102563 35626167 PMC9140192 · DOI
  4. [5]Kilmister E.J. Koh S.P. Weth F.R. Gray C. Tan S.T. Cancer Metastasis and Treatment Resistance: Mechanistic Insights and Therapeutic Targeting of Cancer Stem Cells and the Tumor Microenvironment Biomedicines 2022 10 2988 10.3390/biomedicines10112988 36428556 PMC9687343 · DOI
  5. [6]Palmer A.C. Chidley C. Sorger P.K. A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity Elife 2019 8 e50036 10.7554/eLife.50036 31742555 PMC6897534 · DOI
  6. [7]Talhouk A. McConechy M.K. Leung S. Li-Chang H.H. Kwon J.S. Melnyk N. Yang W. Senz J. Boyd N. Karnezis A.N. A clinically applicable molecular-based classification for endometrial cancers Br. J. Cancer 2015 113 299 310 10.1038/bjc.2015.190 26172027 PMC4506381 · DOI
  7. [8]Mitric C. Bernardini M.Q. Endometrial Cancer: Transitioning from Histology to Genomics Curr. Oncol. 2022 29 741 757 10.3390/curroncol29020063 35200562 PMC8870297 · DOI
  8. [9]Kuhn T.M. Dhanani S. Ahmad S. An Overview of Endometrial Cancer with Novel Therapeutic Strategies Curr. Oncol. 2023 30 7904 7919 10.3390/curroncol30090574 37754489 PMC10528347 · DOI
  9. [10]Vermij L. Smit V. Nout R. Bosse T. Incorporation of molecular characteristics into endometrial cancer management Histopathology 2020 76 52 63 10.1111/his.14015 31846532 PMC6972558 · DOI
  10. [11]Horn L.C. Meinel A. Handzel R. Einenkel J. Histopathology of endometrial hyperplasia and endometrial carcinoma: An update Ann. Diagn. Pathol. 2007 11 297 311 10.1016/j.anndiagpath.2007.05.002 17630117 · DOI
  11. [12]Makker V. MacKay H. Ray-Coquard I. Levine D.A. Westin S.N. Aoki D. Oaknin A. Endometrial cancer Nat. Rev. Dis. Primers 2021 7 88 10.1038/s41572-021-00324-8 34887451 PMC9421940 · DOI
  12. [13]Russell R.G. Xia Z. Dunford J.E. Oppermann U. Kwaasi A. Hulley P.A. Kavanagh K.L. Triffitt J.T. Lundy M.W. Phipps R.J. Bisphosphonates: An update on mechanisms of action and how these relate to clinical efficacy Ann. New York Acad. Sci. 2007 1117 209 257 10.1196/annals.1402.089 18056045 · DOI
  13. [14]Xu Z. Alendronate for the Treatment of Osteoporosis in Men: A Meta-Analysis of Randomized Controlled Trials Am. J. Ther. 2017 24 e130 e138 10.1097/MJT.0000000000000446 27058577 · DOI
  14. [15]Watts N. Freedholm D. Daifotis A. The clinical tolerability profile of alendronate Int. J. Clin. Pract. Suppl. 1999 101 51 61 12669741
  15. [16]Iwamoto J. Takeda T. Sato Y. Efficacy and safety of alendronate and risedronate for postmenopausal osteoporosis Curr. Med. Res. Opin. 2006 22 919 928 10.1185/030079906X100276 16709313 · DOI
  16. [17]Xia Y. Xie Y. Yu Z. Xiao H. Jiang G. Zhou X. Yang Y. Li X. Zhao M. Li L. The Mevalonate Pathway Is a Druggable Target for Vaccine Adjuvant Discovery Cell 2018 175 1059 1073.e21 10.1016/j.cell.2018.08.070 30270039 · DOI
  17. [18]Andela V.B. Pirri M. Schwarz E.M. Puzas E.J. O’Keefe R.J. Rosenblatt J.D. Rosier R.N. The mevalonate synthesis pathway as a therapeutic target in cancer Clin. Orthop. Relat. Res. 2003 415 S59 S66 10.1097/01.blo.0000093846.72468.66 14600593 · DOI
  18. [19]Thurnher M. Nussbaumer O. Gruenbacher G. Novel aspects of mevalonate pathway inhibitors as antitumor agents Clin. Cancer Res. 2012 18 3524 3531 10.1158/1078-0432.CCR-12-0489 22529099 · DOI
  19. [20]Nemoto R. Sato S. Nishijima Y. Miyakawa I. Koiso K. Harada M. Effects of a new bisphosphonate (AHBuBP) on osteolysis induced by human prostate cancer cells in nude mice J. Urol. 1990 144 770 774 10.1016/S0022-5347(17)39589-7 2117674 · DOI
  20. [21]Nemoto R. Satou S. Mochizuki T. Okabe K. Response of MBT-2 bladder carcinoma-induced osteolysis to various agents Cancer 1992 69 2316 2321 10.1002/1097-0142(19920501)69:9<2316::AID-CNCR2820690919>3.0.CO;2-8 1562978 · DOI
  21. [22]Kim H.Y. Kim D.K. Bae S.H. Gwak H. Jeon J.H. Kim J.K. Lee B.I. You H.J. Shin D.H. Kim Y.H. Farnesyl diphosphate synthase is important for the maintenance of glioblastoma stemness Exp. Mol. Med. 2018 50 1 12 10.1038/s12276-018-0166-2 30333528 PMC6193020 · DOI
  22. [23]Souchek J.J. Baine M.J. Lin C. Rachagani S. Gupta S. Kaur S. Lester K. Zheng D. Chen S. Smith L. Unbiased analysis of pancreatic cancer radiation resistance reveals cholesterol biosynthesis as a novel target for radiosensitisation Br. J. Cancer 2014 111 1139 1149 10.1038/bjc.2014.385 25025965 PMC4453840 · DOI
  23. [24]Parente-Pereira A.C. Shmeeda H. Whilding L.M. Zambirinis C.P. Foster J. van der Stegen S.J. Beatson R. Zabinski T. Brewig N. Sosabowski J.K. Adoptive immunotherapy of epithelial ovarian cancer with Vγ9Vδ2 T cells, potentiated by liposomal alendronic acid J. Immunol. 2014 193 5557 5566 10.4049/jimmunol.1402200 25339667 · DOI
  24. [25]Sun S. Meng Y. Li M. Tang X. Hu W. Wu W. Li G. Pang Q. Wang W. Liu B. CD133+ endothelial-like stem cells restore neovascularization and promote longevity in progeroid and naturally aged mice Nat. Aging. 2023 3 1401 1414 10.1038/s43587-023-00512-z 37946040 PMC10645602 · DOI
  25. [26]Gao S. Soares F. Wang S. Wong C.C. Chen H. Yang Z. Liu W. Go M.Y.Y. Ahmed M. Zeng Y. CRISPR screens identify cholesterol biosynthesis as a therapeutic target on stemness and drug resistance of colon cancer Oncogene 2021 40 6601 6613 10.1038/s41388-021-01882-7 34621019 PMC8639446 · DOI
  26. [27]Chiarella E. Nisticò C. Di Vito A. Morrone H.L. Mesuraca M. Targeting of Mevalonate-Isoprenoid Pathway in Acute Myeloid Leukemia Cells by Bisphosphonate Drugs Biomedicines 2022 10 1146 10.3390/biomedicines10051146 35625883 PMC9138592 · DOI
  27. [28]Chiarella E. Codispoti B. Aloisio A. Cosentino E.G. Scicchitano S. Montalcini Y. Lico D. Morrone G. Mesuraca M. Bond H.M. Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells Heliyon 2020 6 e04020 10.1016/j.heliyon.2020.e04020 32529062 PMC7283156 · DOI
  28. [29]Gehrke B. Alves Coelho M.C. Brasil d’Alva C. Madeira M. Long-term consequences of osteoporosis therapy with bisphosphonates Arch. Endocrinol. Metab. 2023 68 e220334 10.20945/2359-4292-2022-0334 37948565 PMC10916794 · DOI
  29. [30]Eiken P.A. Prieto-Alhambra D. Eastell R. Abrahamsen B. Surgically treated osteonecrosis and osteomyelitis of the jaw and oral cavity in patients highly adherent to alendronate treatment: A nationwide user-only cohort study including over 60,000 alendronate users Osteoporos. Int. 2017 28 2921 2928 10.1007/s00198-017-4132-y 28664276 · DOI
  30. [31]Zhang X.S. Zhang Y.M. Li B. Fan B. Zhao Y. Yang S.J. Risk reduction of endometrial and ovarian cancer after bisphosphonates use: A meta-analysis Gynecol. Oncol. 2018 150 509 514 10.1016/j.ygyno.2018.06.012 29960711 · DOI
  31. [32]Rennert G. Rennert H.S. Pinchev M. Lavie O. The effect of bisphosphonates on the risk of endometrial and ovarian malignancies Gynecol. Oncol. 2014 133 309 313 10.1016/j.ygyno.2014.02.014 24556062 · DOI
  32. [33]Newcomb P.A. Passarelli M.N. Phipps A.I. Anderson G.L. Wactawski-Wende J. Ho G.Y. O’Sullivan M.J. Chlebowski R.T. Oral bisphosphonate use and risk of postmenopausal endometrial cancer J. Clin. Oncol. 2015 33 1186 1190 10.1200/JCO.2014.58.6842 25713431 PMC4372855 · DOI
  33. [34]Alford S.H. Rattan R. Buekers T.E. Munkarah A.R. Protective effect of bisphosphonates on endometrial cancer incidence in data from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial Cancer 2015 121 441 447 10.1002/cncr.28952 25533883 · DOI
  34. [35]Ou Y.J. Chiu H.F. Wong Y.H. Yang Y.H. Bisphosphonate use and the risk of endometrial cancer: A meta-analysis of observational studies Pharmacoepidemiol. Drug Saf. 2016 25 1107 1115 10.1002/pds.4075 27501339 · DOI
  35. [36]Deng Y. Zhang Z. Jia X. Cheng W. Zhou X. Liu Y. Wang M. Oral bisphosphonates and incidence of cancers in patients with osteoporosis: A systematic review and meta-analysis Arch. Osteoporos. 2018 14 1 10.1007/s11657-018-0552-3 30560459 · DOI
  36. [37]Mathew A. Brufsky A. Decreased risk of breast cancer associated with oral bisphosphonate therapy Breast Cancer 2012 4 75 81 10.2147/BCTT.S16356 24367195 PMC3846467 · DOI
  37. [38]Li Y.Y. Gao L.J. Zhang Y.X. Liu S.J. Cheng S. Liu Y.P. Jia C.X. Bisphosphonates and risk of cancers: A systematic review and meta-analysis Br. J. Cancer 2020 123 1570 1581 10.1038/s41416-020-01043-9 32901134 PMC7652831 · DOI
  38. [39]La-Beck N.M. Liu X. Shmeeda H. Shudde C. Gabizon A.A. Repurposing amino-bisphosphonates by liposome formulation for a new role in cancer treatment Semin. Cancer Biol. 2021 68 175 185 10.1016/j.semcancer.2019.12.001 31874280 · DOI
  39. [40]Hodgins N.O. Al-Jamal W.T. Wang J.T. Parente-Pereira A.C. Liu M. Maher J. Al-Jamal K.T. In vitro potency, in vitro and in vivo efficacy of liposomal alendronate in combination with γδ T cell immunotherapy in mice J. Control. Release 2016 241 229 241 10.1016/j.jconrel.2016.09.023 27664328 PMC5073077 · DOI
  40. [41]Al Barashdi M.A.S. Ali A. McMullin M.F. Mills K. CD45 inhibition in myeloid leukaemia cells sensitizes cellular responsiveness to chemotherapy Ann. Hematol. 2024 103 73 88 10.1007/s00277-023-05520-y 37917373 PMC10761371 · DOI
  41. [42]Thamake S.I. Raut S.L. Gryczynski Z. Ranjan A.P. Vishwanatha J.K. Alendronate coated poly-lactic-co-glycolic acid (PLGA) nanoparticles for active targeting of metastatic breast cancer Biomaterials 2012 33 7164 7173 10.1016/j.biomaterials.2012.06.026 22795543 · DOI
  42. [43]Vinogradova Y. Coupland C. Hippisley-Cox J. Exposure to bisphosphonates and risk of common non-gastrointestinal cancers: Series of nested case-control studies using two primary-care databases Br. J. Cancer 2013 109 795 806 10.1038/bjc.2013.383 23868009 PMC3738131 · DOI
  43. [44]Susa M. Morii T. Yabe H. Horiuchi K. Toyama Y. Weissbach L. Hornicek F.J. Morioka H. Alendronate inhibits growth of high-grade chondrosarcoma cells Anticancer Res. 2009 29 1879 1888 19528443
  44. [45]Yang G. Hu H. Zeng R. Huang J. Oral bisphosphonates and the risk of colorectal cancer: A meta-analysis J. Clin. Gastroenterol. 2013 47 741 748 10.1097/MCG.0b013e31829e446b 24030705 · DOI
  45. [46]Heikkilä P. Teronen O. Moilanen M. Konttinen Y.T. Hanemaaijer R. Laitinen M. Maisi P. van der Pluijm G. Bartlett J.D. Salo T. Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines Anticancer Drugs 2002 13 245 254 10.1097/00001813-200203000-00006 11984068 · DOI
  46. [47]Abrahamsen B. Pazianas M. Eiken P. Russell R.G. Eastell R. Esophageal and gastric cancer incidence and mortality in alendronate users J. Bone Miner. Res. 2012 27 679 686 10.1002/jbmr.1481 22113985 · DOI
  47. [48]Deslivia M.F. Savio S.D. Wiratnaya I. Astawa P. Sandiwidayat K.S. Bimantara N.G. The Efficacy of Bisphosphonate in the Treatment of Giant Cell Tumour of the Bone: A Systematic Review and Meta-Analysis Malays. Orthop. J. 2023 17 98 110 10.5704/MOJ.2303.012 37064619 PMC10103925 · DOI
  48. [49]Ilyas A. Hashim Z. Channa I.S. Zarina S. Alendronate and FTI-277 combination as a possible therapeutic approach for hepatocellular carcinoma: An in vitro study Hepatobiliary Pancreat. Dis. Int. 2018 17 241 250 10.1016/j.hbpd.2018.03.013 29627155 · DOI
  49. [50]Kunzmann V. Bauer E. Feurle J. Weissinger F. Tony H.P. Wilhelm M. Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma Blood 2000 96 384 392 10.1182/blood.V96.2.384.013k07_384_392 10887096 · DOI
  50. [51]Açil Y. Möller B. Niehoff P. Rachko K. Gassling V. Wiltfang J. Simon M.J. The cytotoxic effects of three different bisphosphonates in-vitro on human gingival fibroblasts, osteoblasts and osteogenic sarcoma cells J. Craniomaxillofac. Surg. 2012 40 e229 e235 10.1016/j.jcms.2011.10.024 22082730 · DOI
  51. [52]Teronen O. Heikkilä P. Konttinen Y.T. Laitinen M. Salo T. Hanemaaijer R. Teronen A. Maisi P. Sorsa T. MMP inhibition and downregulation by bisphosphonates Ann. New York Acad. Sci. 1999 878 453 465 10.1111/j.1749-6632.1999.tb07702.x 10415748 · DOI
  52. [53]Lai T.J. Hsu S.F. Li T.M. Hsu H.C. Lin J.G. Hsu C.J. Chou M.C. Lee M.C. Yang S.F. Fong Y.C. Alendronate inhibits cell invasion and MMP-2 secretion in human chondrosarcoma cell line Acta Pharmacol. Sin. 2007 28 1231 1235 10.1111/j.1745-7254.2007.00607.x 17640487 · DOI
  53. [54]Cheng Y.Y. Huang L. Lee K.M. Li K. Kumta S.M. Alendronate regulates cell invasion and MMP-2 secretion in human osteosarcoma cell lines Pediatr. Blood Cancer 2004 42 410 415 10.1002/pbc.20019 15049011 · DOI
  54. [55]Farina A.R. Cappabianca L. Di Ianni N. Ruggeri P. Ragone M. Merolle S. Gulino A. Mackay A.R. Alendronate promotes plasmin-mediated MMP-9 inactivation by exposing cryptic plasmin degradation sites within the MMP-9 catalytic domain FEBS Lett. 2012 586 2366 2374 10.1016/j.febslet.2012.05.048 22677171 · DOI
  55. [56]Liu C. Li Y. Hu S. Chen Y. Gao L. Liu D. Guo H. Yang Y. Clinical significance of matrix metalloproteinase-2 in endometrial cancer: A systematic review and meta-analysis Medicine 2018 97 e10994 10.1097/MD.0000000000010994 30024495 PMC6086493 · DOI
  56. [57]Mahecha A.M. Wang H. The influence of vascular endothelial growth factor-A and matrix metalloproteinase-2 and -9 in angiogenesis, metastasis, and prognosis of endometrial cancer OncoTargets Ther. 2017 10 4617 4624 10.2147/OTT.S132558 PMC5614795 29033580 · DOI
  57. [58]Yu F. Jiang Q. Zhou Y. Yang Z. Yu X. Wang H. Liu Z. Wang L. Fang W. Guo S. Abnormal expression of matrix metalloproteinase-9 (MMP9) correlates with clinical course in Chinese patients with endometrial cancer Dis. Markers 2012 32 321 327 10.1155/2012/269279 22674412 PMC3826421 · DOI
  58. [59]Jedryka M. Chrobak A. Chelmonska-Soyta A. Gawron D. Halbersztadt A. Wojnar A. Kornafel J. Matrix metalloproteinase (MMP)-2 and MMP-9 expression in tumor infiltrating CD3 lymphocytes from women with endometrial cancer Int. J. Gynecol. Cancer 2012 22 1303 1309 10.1097/IGC.0b013e318269e27b 22964525 · DOI
  59. [60]Zhang Y. Zheng W. Shen K. Shen W. ∆9-tetrahydrocannabinol inhibits epithelial-mesenchymal transition and metastasis by targeting matrix metalloproteinase-9 in endometrial cancer Oncol. Lett. 2018 15 8527 8535 10.3892/ol.2018.8407 29805589 PMC5950514 · DOI
  60. [61]Das S. Amin S.A. Jha T. Inhibitors of gelatinases (MMP-2 and MMP-9) for the management of hematological malignancies Eur. J. Med. Chem. 2021 223 113623 10.1016/j.ejmech.2021.113623 34157437 · DOI
  61. [62]Cabral-Pacheco G.A. Garza-Veloz I. Castruita-De la Rosa C. Ramirez-Acuña J.M. Perez-Romero B.A. Guerrero-Rodriguez J.F. Martinez-Avila N. Martinez-Fierro M.L. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases Int. J. Mol. Sci. 2020 21 9739 10.3390/ijms21249739 33419373 PMC7767220 · DOI · Paper page
  62. [63]Sawada K. Morishige K. Mabuchi S. Ogata S. Kawase C. Sakata M. Kimura T. In vitro and in vivo assays to analyze the contribution of Rho kinase in angiogenesis Methods Enzymol. 2008 439 395 412 10.1016/S0076-6879(07)00428-4 18374179 · DOI
  63. [64]Sawada K. Morishige K. Tahara M. Kawagishi R. Ikebuchi Y. Tasaka K. Murata Y. Alendronate inhibits lysophosphatidic acid-induced migration of human ovarian cancer cells by attenuating the activation of rho Cancer Res. 2002 62 6015 6020 12414621
  64. [65]Hashimoto K. Morishige K. Sawada K. Tahara M. Shimizu S. Ogata S. Sakata M. Tasaka K. Kimura T. Alendronate suppresses tumor angiogenesis by inhibiting Rho activation of endothelial cells Biochem. Biophys. Res. Commun. 2007 354 478 484 10.1016/j.bbrc.2007.01.014 17240356 · DOI
  65. [66]Ye Y. Lv X. Wang M.H. Zhu J. Chen S.Q. Jiang C.Y. Fu G.S. Alendronate prevents angiotensin II-induced collagen I production through geranylgeranylation-dependent RhoA/Rho kinase activation in cardiac fibroblasts J. Pharmacol. Sci. 2015 129 205 209 10.1016/j.jphs.2015.10.006 26627555 · DOI
  66. [67]Hashimoto K. Morishige K. Sawada K. Tahara M. Kawagishi R. Ikebuchi Y. Sakata M. Tasaka K. Murata Y. Alendronate inhibits intraperitoneal dissemination in in vivo ovarian cancer model Cancer Res. 2005 65 540 545 10.1158/0008-5472.540.65.2 15695397 · DOI
  67. [68]Wei L. Surma M. Shi S. Lambert-Cheatham N. Shi J. Novel Insights into the Roles of Rho Kinase in Cancer Arch. Immunol. Ther. Exp. 2016 64 259 1278 10.1007/s00005-015-0382-6 PMC4930737 26725045 · DOI
  68. [69]Zubor P. Dankova Z. Kolkova Z. Holubekova V. Brany D. Mersakova S. Samec M. Liskova A. Koklesova L. Kubatka P. Rho GTPases in Gynecologic Cancers: In-Depth Analysis toward the Paradigm Change from Reactive to Predictive, Preventive, and Personalized Medical Approach Benefiting the Patient and Healthcare Cancers 2020 12 1292 10.3390/cancers12051292 32443784 PMC7281750 · DOI
  69. [70]Yagi H. Onoyama I. Asanoma K. Kawakami M. Maenohara S. Kodama K. Matsumura Y. Hamada N. Hori E. Hachisuga K. Tumor-derived ARHGAP35 mutations enhance the Gα13-Rho signaling axis in human endometrial cancer Cancer Gene. Ther. 2023 30 313 323 10.1038/s41417-022-00547-1 36257976 · DOI
  70. [71]Marhaba Anjum S. Mandal P. Agrawal S. Ansari K.M. Zearalenone promotes endometrial cancer cell migration and invasion via activation of estrogen receptor-mediated Rho/ROCK/PMLC signaling pathway Food Chem. Toxicol. 2024 193 115017 10.1016/j.fct.2024.115017 39306225 · DOI
  71. [72]Zhang C. Zhang H. Yang X. Li S. Wang L. Su H. Yang J. Ding Y. Zhang X. Qiang B. MYO3B promotes cancer progression in endometrial cancer by mediating the calcium ion-RhoA/ROCK1 signaling pathway J. Cancer Res. Clin. Oncol. 2024 150 424 10.1007/s00432-024-05940-x 39297944 PMC11413061 · DOI
  72. [73]Wen X. Wan J. He Q. Wang M. Li S. Jiang M. Qian Z. Liu B. Lu W. Wang K. p190A inactivating mutations cause aberrant RhoA activation and promote malignant transformation via the Hippo-YAP pathway in endometrial cancer Signal Transduct. Target. Ther. 2020 5 81 10.1038/s41392-020-0170-6 32457342 PMC7250911 · DOI
  73. [74]Li X. Cheng Y. Wang Z. Zhou J. Jia Y. He X. Zhao L. Dong Y. Fan Y. Yang X. Calcium and TRPV4 promote metastasis by regulating cytoskeleton through the RhoA/ROCK1 pathway in endometrial cancer Cell Death Dis. 2020 11 1009 10.1038/s41419-020-03181-7 33230171 PMC7683721 · DOI
  74. [75]Hayday A. Dechanet-Merville J. Rossjohn J. Silva-Santos B. Cancer immunotherapy by gamma-delta T cells Science 2024 386 eabq7248 10.1126/science.abq7248 39361750 PMC7616870 · DOI
  75. [76]Zou C. Zhao P. Xiao Z. Han X. Fu F. Fu L. gamma-delta T cells in cancer immunotherapy Oncotarget 2017 8 8900 8909 10.18632/oncotarget.13051 27823972 PMC5352452 · DOI
  76. [77]Revesz I.A. Joyce P. Ebert L.M. Prestidge C.A. Effective gamma-delta T-cell clinical therapies: Current limitations and future perspectives for cancer immunotherapy Clin. Transl. Immunol. 2024 13 e1492 10.1002/cti2.1492 PMC10875631 38375329 · DOI
  77. [78]Silva-Santos B. Serre K. Norell H. gamma-delta T cells in cancer Nat. Rev. Immunol. 2015 15 683 691 10.1038/nri3904 26449179 · DOI · Paper page
  78. [79]Liu J. Chen X. Jiang Y. Cheng W. Development of an immune gene prognostic classifier for survival prediction and respond to immunocheckpoint inhibitor therapy/chemotherapy in endometrial cancer Int. Immunopharmacol. 2020 86 106735 10.1016/j.intimp.2020.106735 32619957 · DOI
  79. [80]Wang J. Lin C. Li H. Li R. Wu Y. Liu H. Zhang H. He H. Zhang W. Xu J. Tumor-infiltrating γδT cells predict prognosis and adjuvant chemotherapeutic benefit in patients with gastric cancer Oncoimmunology 2017 6 e1353858 10.1080/2162402X.2017.1353858 29147601 PMC5674957 · DOI
  80. [81]Meraviglia S. Lo Presti E. Tosolini M. La Mendola C. Orlando V. Todaro M. Catalano V. Stassi G. Cicero G. Vieni S. Distinctive features of tumor-infiltrating γδ T lymphocytes in human colorectal cancer Oncoimmunology 2017 6 e1347742 10.1080/2162402X.2017.1347742 29123962 PMC5665062 · DOI
  81. [82]Donia M. Ellebaek E. Andersen M.H. Straten P.T. Svane I.M. Analysis of Vδ1 T Cells in Clinical Grade Melanoma-Infiltrating Lymphocytes OncoImmunology 2012 1 1297 1304 10.4161/onci.21659 23243593 PMC3518502 · DOI
  82. [83]Lu H. Dai W. Guo J. Wang D. Wen S. Yang L. Lin D. Xie W. Wen L. Fang J. High Abundance of Intratumoral γδ T Cells Favors a Better Prognosis in Head and Neck Squamous Cell Carcinoma: A Bioinformatic Analysis Front. Immunol. 2020 11 573920 10.3389/fimmu.2020.573920 33101298 PMC7555127 · DOI
  83. [84]Zhao N. Dang H. Ma L. Martin S.P. Forgues M. Ylaya K. Hewitt S.M. Wang X.W. Intratumoral γδ T-Cell Infiltrates, Chemokine (C-C Motif) Ligand 4/Chemokine (C-C Motif) Ligand 5 Protein Expression and Survival in Patients With Hepatocellular Carcinoma Hepatology 2021 73 1045 1060 10.1002/hep.31412 32502310 PMC9175512 · DOI
  84. [85]Gentles A.J. Newman A.M. Liu C.L. Bratman S.V. Feng W. Kim D. Nair V.S. Xu Y. Khuong A. Hoang C.D. The prognostic landscape of genes and infiltrating immune cells across human cancers Nat. Med. 2015 21 938 945 10.1038/nm.3909 26193342 PMC4852857 · DOI
  85. [86]Tosolini M. Pont F. Poupot M. Vergez F. Nicolau-Travers M.L. Vermijlen D. Sarry J.E. Dieli F. Fournié J.J. Assessment of tumor-infiltrating TCRVγ9Vδ2 γδ lymphocyte abundance by deconvolution of human cancers microarrays Oncoimmunology 2017 6 e1284723 10.1080/2162402X.2017.1284723 28405516 PMC5384348 · DOI
  86. [87]Saura-Esteller J. de Jong M. King L.A. Ensing E. Winograd B. de Gruijl T.D. Parren P.W.H.I. van der Vliet H.J. Gamma Delta T-Cell Based Cancer Immunotherapy: Past-Present-Future Front. Immunol. 2022 13 915837 10.3389/fimmu.2022.915837 35784326 PMC9245381 · DOI
  87. [88]Costa G.P. Mensurado S. Silva-Santos B. Therapeutic avenues for γδ T cells in cancer J. Immunother. Cancer 2023 11 e007955 10.1136/jitc-2023-007955 38007241 PMC10680012 · DOI
  88. [89]Li Y. Mo X.P. Yao H. Xiong Q.X. Research Progress of γδT Cells in Tumor Immunotherapy Cancer Control 2024 31 10732748241284863 10.1177/10732748241284863 39348473 PMC11459529 · DOI
  89. [90]Fonseca S. Pereira V. Lau C. Teixeira M.D.A. Bini-Antunes M. Lima M. Human Peripheral Blood Gamma Delta T Cells: Report on a Series of Healthy Caucasian Portuguese Adults and Comprehensive Review of the Literature Cells 2020 9 729 10.3390/cells9030729 32188103 PMC7140678 · DOI
  90. [91]Yuan M. Wang W. Hawes I. Han J. Yao Z. Bertaina A. Advancements in gamma-delta T cell engineering: Paving the way for enhanced cancer immunotherapy Front. Immunol. 2024 15 1360237 10.3389/fimmu.2024.1360237 38576617 PMC10991697 · DOI
  91. [92]Wiesheu R. Coffelt S.B. From backstage to the spotlight: γδT cells in cancer Cancer Cell 2024 42 1637 1642 10.1016/j.ccell.2024.08.017 39270647 · DOI
  92. [93]Nagamine I. Yamaguchi Y. Ohara M. Ikeda T. Okada M. Induction of gamma delta T cells using zoledronate plus interleukin-2 in patients with metastatic cancer Hiroshima. J. Med. Sci. 2009 58 37 44 19400555
  93. [94]Arias-Badia M. Chang R. Fong L. Gamma-delta T cells as critical anti-tumor immune effectors Nat. Cancer. 2024 5 1145 1157 10.1038/s43018-024-00798-x 39060435 · DOI
  94. [95]Kunzmann V. Smetak M. Kimmel B. Weigang-Koehler K. Goebeler M. Birkmann J. Becker J. Schmidt-Wolf I.G. Einsele H. Wilhelm M. Tumor-promoting versus tumor-antagonizing roles of gamma-delta T cells in cancer immunotherapy: Results from a prospective phase I/II trial J. Immunother. 2012 35 205 213 10.1097/CJI.0b013e318245bb1e 22306909 · DOI
  95. [96]Noguchi A. Kaneko T. Kamigaki T. Fujimoto K. Ozawa M. Saito M. Ariyoshi N. Goto S. Zoledronate-activated Vγ9gamma-delta T cell-based immunotherapy is feasible and restores the impairment of gamma-delta T cells in patients with solid tumors Cytotherapy 2011 13 92 97 10.3109/14653249.2010.515581 20831354 · DOI
  96. [97]Abe Y. Muto M. Nieda M. Nakagawa Y. Nicol A. Kaneko T. Goto S. Yokokawa K. Suzuki K. Clinical and immunological evaluation of zoledronate-activated Vgamma9gammadelta T-cell-based immunotherapy for patients with multiple myeloma Exp. Hematol. 2009 37 956 968 10.1016/j.exphem.2009.04.008 19409955 · DOI
  97. [98]Pressey J.G. Adams J. Harkins L. Kelly D. You Z. Lamb L.S. Jr. In vivo expansion and activation of gamma-delta T cells as immunotherapy for refractory neuroblastoma: A phase 1 study Medicine 2016 95 e4909 10.1097/MD.0000000000004909 27684826 PMC5265919 · DOI
  98. [99]Meraviglia S. Eberl M. Vermijlen D. Todaro M. Buccheri S. Cicero G. La Mendola C. Guggino G. D’Asaro M. Orlando V. In vivo manipulation of Vgamma9Vdelta2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients Clin. Exp. Immunol. 2010 161 290 297 10.1111/j.1365-2249.2010.04167.x 20491785 PMC2909411 · DOI
  99. [100]Rossini M. Adami S. Viapiana O. Fracassi E. Ortolani R. Vella A. Zanotti R. Tripi G. Idolazzi L. Gatti D. Long-term effects of amino-bisphosphonates on circulating gamma-delta T cells Calcif. Tissue Int. 2012 91 395 399 10.1007/s00223-012-9647-9 23052225 · DOI
  100. [101]Gutman D. Epstein-Barash H. Tsuriel M. Golomb G. Alendronate liposomes for antitumor therapy: Activation of gamma-delta T cells and inhibition of tumor growth Adv. Exp. Med. Biol. 2012 733 165 179 10.1007/978-94-007-2555-3_16 22101722 · DOI
  101. [102]Cairo C. Sagnia B. Cappelli G. Colizzi V. Leke R.G. Leke R.J. Pauza C.D. Human cord blood gamma-delta T cells expressing public Vγ2 chains dominate the response to bisphosphonate plus interleukin-15 Immunology 2013 138 346 360 10.1111/imm.12039 23181340 PMC3719945 · DOI
  102. [103]Ferlazzo V. Sferrazza C. Caccamo N. Di Fede G. Di Lorenzo G. D’Asaro M. Meraviglia S. Dieli F. Rini G. Salerno A. In vitro effects of aminobisphosphonates on Vgamma9Vdelta2 T cell activation and differentiation Int. J. Immunopathol. Pharmacol. 2006 19 309 317 10.1177/039463200601900208 16831298 · DOI
  103. [104]Thompson K. Roelofs A.J. Jauhiainen M. Mönkkönen H. Mönkkönen J. Rogers M.J. Activation of gamma-delta T cells by bisphosphonates Adv. Exp. Med. Biol. 2010 658 11 20 10.1007/978-1-4419-1050-9_2 19950011 · DOI
  104. [105]Mao T.L. Miao C.H. Liao Y.J. Chen Y.J. Yeh C.Y. Liu C.L. Ex Vivo Expanded Human Vγ9Vδ2 T-Cells Can Suppress Epithelial Ovarian Cancer Cell Growth Int. J. Mol. Sci. 2019 20 1139 10.3390/ijms20051139 30845699 PMC6429417 · DOI
  105. [106]Kondo M. Sakuta K. Noguchi A. Ariyoshi N. Sato K. Sato S. Sato K. Hosoi A. Nakajima J. Yoshida Y. Zoledronate facilitates large-scale ex vivo expansion of functional gammadelta T cells from cancer patients for use in adoptive immunotherapy Cytotherapy 2008 10 842 856 10.1080/14653240802419328 19016372 · DOI
  106. [107]Cabillic F. Toutirais O. Lavoué V. de La Pintière C.T. Daniel P. Rioux-Leclerc N. Turlin B. Mönkkönen H. Mönkkönen J. Boudjema K. Aminobisphosphonate-pretreated dendritic cells trigger successful Vgamma9Vdelta2 T cell amplification for immunotherapy in advanced cancer patients Cancer Immunol. Immunother. 2010 59 1611 1619 10.1007/s00262-010-0887-0 20582413 PMC11030894 · DOI
  107. [108]Benzaïd I. Mönkkönen H. Stresing V. Bonnelye E. Green J. Mönkkönen J. Touraine J.L. Clézardin P. High phosphoantigen levels in bisphosphonate-treated human breast tumors promote Vgamma9Vdelta2 T-cell chemotaxis and cytotoxicity in vivo Cancer Res. 2011 71 4562 4572 10.1158/0008-5472.CAN-10-3862 21646473 · DOI
  108. [109]Das H. Wang L. Kamath A. Bukowski J.F. Vgamma2Vdelta2 T-cell receptor-mediated recognition of aminobisphosphonates Blood. 2001 98 1616 1618 10.1182/blood.V98.5.1616 11520816 · DOI
  109. [110]Shaheen M.Y. Basudan A.M. Niazy A.A. van den Beucken J.J.J.P. Jansen J.A. Alghamdi H.S. Impact of Single or Combined Drug Therapy on Bone Regeneration in Healthy and Osteoporotic Rats Tissue Eng. Part A 2021 27 572 581 10.1089/ten.tea.2020.0122 32838702 · DOI
  110. [111]Anbinder A.L. Prado Fde A. Prado Mde A. Balducci I. Rocha R.F. The influence of ovariectomy, simvastatin and sodium alendronate on alveolar bone in rats Braz. Oral Res. 2007 21 247 252 10.1590/S1806-83242007000300010 17710291 · DOI
  111. [112]Mohamed M.T. Abuelezz S.A. Atalla S.S. El Aziz L.F.A. Gorge S.S. The anti-osteoporotic and anti-atherogenic effects of alendronate and simvastatin in ovariectomized rats fed high fat diet: A comparative study of combination therapy versus monotherapy Biomed. Pharmacother. 2017 89 1115 1124 10.1016/j.biopha.2017.02.105 28298072 · DOI
  112. [113]Apostu D. Lucaciu O. Mester A. Oltean-Dan D. Gheban D. Rares Ciprian Benea H. Tibolone, alendronate, and simvastatin enhance implant osseointegration in a preclinical in vivo model Clin. Oral Implants Res. 2020 31 655 668 10.1111/clr.13602 32279374 · DOI
  113. [114]Yoon L.S. Goodman M.T. Rimel B.J. Jeon C.Y. Statin use and survival in elderly patients with endometrial cancer Gynecol. Oncol. 2015 137 252 257 10.1016/j.ygyno.2015.01.549 25666607 · DOI
  114. [115]Diniz J.A. Dourado A.C.A.G. Barbirato D.D.S. da Silveira K.G. Vasconcellos R.J.H. Laureano Filho J.R. Effect of simvastatin topical use on alveolar bone after tooth extraction: A scoping review Clin. Oral Investig. 2024 28 86 10.1007/s00784-023-05482-5 38195898 · DOI
  115. [116]Li Z.H. Li C. Szajnman S.H. Rodriguez J.B. Moreno S.N.J. Synergistic Activity between Statins and Bisphosphonates against Acute Experimental Toxoplasmosis Antimicrob. Agents Chemother. 2017 61 e02628-16 10.1128/AAC.02628-16 28559264 PMC5527628 · DOI
  116. [117]Issat T. Nowis D. Legat M. Makowski M. Klejman M.P. Urbanski J. Skierski J. Koronkiewicz M. Stoklosa T. Brzezinska A. Potentiated antitumor effects of the combination treatment with statins and pamidronate in vitro and in vivo Int. J. Oncol. 2007 30 1413 1425 10.3892/ijo.30.6.1413 17487362 · DOI
  117. [118]Elsayed M. Kobayashi D. Kubota T. Matsunaga N. Murata R. Yoshizawa Y. Watanabe N. Matsuura T. Tsurudome Y. Ogino T. Synergistic Antiproliferative Effects of Zoledronic Acid and Fluvastatin on Human Pancreatic Cancer Cell Lines: An in Vitro Study Biol. Pharm. Bull. 2016 39 1238 1246 10.1248/bpb.b15-00746 27181081 · DOI
  118. [119]Nishiguchi T. Akiyoshi T. Anami S. Nakabayashi T. Matsuyama K. Matzno S. Synergistic action of statins and nitrogen-containing bisphosphonates in the development of rhabdomyolysis in L6 rat skeletal myoblasts J. Pharm. Pharmacol. 2009 61 781 788 10.1211/jpp.61.06.0011 19505369 · DOI
  119. [120]Kawashiri T. Tokunaga A. Kobayashi D. Shimazoe T. Anti-tumor Activities of 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase Inhibitors and Bisphosphonates in Pancreatic Cell Lines Which Show Poor Responses to Gemcitabine Biol. Pharm. Bull. 2020 43 49 52 10.1248/bpb.b19-00435 31902931 · DOI
  120. [121]Xiong Z. Yi P. Tang X. Shu L. Zhang C. Meta-Analysis of the Efficacy and Safety of Alendronate Combined with Atorvastatin in the Treatment of Osteoporosis in Diabetes Mellitus Biomed. Res. Int. 2022 2022 6747469 10.1155/2022/6747469 35178452 PMC8844385 · DOI
  121. [122]Rogers M. Kalra S. Moukharskaya J. Chakraborty K. Niyazi M. Krishnan K. Lightner J. Brannon M. Stone W.L. Palau V.E. Synergistic growth inhibition of PC3 prostate cancer cells with low-dose combinations of simvastatin and alendronate Anticancer Res. 2015 35 1851 1859 25862838
  122. [123]Bandgar S.A. Jadhav N.R. Manjappa A.S. A remarkable in vitro cytotoxic, cell cycle arresting and proapoptotic characteristics of low-dose mixed micellar simvastatin combined with alendronate sodium Drug. Deliv. Transl. Res. 2020 10 1122 1135 10.1007/s13346-020-00752-1 32221848 · DOI
  123. [124]Sequetto P.L. Gonçalves R.V. Pinto A.S. Oliveira M.G.A. Maldonado I.R.S.C. Oliveira T.T. Novaes R.D. Low Doses of Simvastatin Potentiate the Effect of Sodium Alendronate in Inhibiting Bone Resorption and Restore Microstructural and Mechanical Bone Properties in Glucocorticoid-Induced Osteoporosis Microsc. Microanal. 2017 23 989 1001 10.1017/S1431927617012363 28743325 · DOI
  124. [125]Nagashima M. Takahashi H. Shimane K. Nagase Y. Wauke K. Osteogenesis and osteoclast inhibition in rheumatoid arthritis patients treated with bisphosphonates alone or in combination with pitavastatin over an 18-month follow-up after more than 4 years of treatment with bisphosphonates Arthritis Res. Ther. 2012 14 R224 10.1186/ar4063 23079134 PMC3580535 · DOI
  125. [126]Schneiders F.L. Huijts C.M. Reijm M. Bontkes H.J. Verheul H.M.W. de Gruijl T.D. van der Vliet H.J. The effects of systemic treatment with aminobisphosphonates and statins on circulating Vγ9Vδ2-T cells in patients with advanced cancer Immunobiology 2018 223 171 177 10.1016/j.imbio.2017.10.029 29055564 · DOI
  126. [127]Von Minckwitz G. Möbus V. Schneeweiss A. Huober J. Thomssen C. Untch M. Jackisch C. Diel I.J. Elling D. Conrad B. German adjuvant intergroup node-positive study: A phase III trial to compare oral ibandronate versus observation in patients with high-risk early breast cancer J. Clin. Oncol. 2013 31 3531 3539 10.1200/JCO.2012.47.2167 23980081 · DOI
  127. [128]Kast R.E. Adding high-dose celecoxib to increase effectiveness of standard glioblastoma chemoirradiation Ann. Pharm. Fr. 2021 79 481 488 10.1016/j.pharma.2021.03.001 33689795 · DOI
  128. [129]Mahboubi-Rabbani M. Zarghi A. Dual Human Carbonic Anhydrase/Cyclooxygenase-2 Inhibitors: A Promising Approach for Cancer Treatment Anticancer Agents Med. Chem. 2021 21 2163 2180 10.2174/1871520621666210129093116 33511940 · DOI
  129. [130]Hashemi Goradel N. Najafi M. Salehi E. Farhood B. Mortezaee K. Cyclooxygenase-2 in cancer: A review J. Cell Physiol. 2019 234 5683 5699 10.1002/jcp.27411 30341914 · DOI
  130. [131]De Monte C. Carradori S. Gentili A. Mollica A. Trisciuoglio D. Supuran C.T. Dual Cyclooxygenase and Carbonic Anhydrase Inhibition by Nonsteroidal Anti-Inflammatory Drugs for the Treatment of Cancer Curr. Med. Chem. 2015 22 2812 2818 10.2174/0929867322666150716113501 26180003 · DOI
  131. [132]Tołoczko-Iwaniuk N. Dziemiańczyk-Pakieła D. Nowaszewska B.K. Celińska-Janowicz K. Miltyk W. Celecoxib in Cancer Therapy and Prevention—Review Curr. Drug Targets 2019 20 302 315 10.2174/1389450119666180803121737 30073924 · DOI
  132. [133]Bąk U. Krupa A. Challenges and Opportunities for Celecoxib Repurposing Pharm. Res. 2023 40 2329 2345 10.1007/s11095-023-03571-4 37552383 PMC10661717 · DOI
  133. [134]Li L. Zhang Y. Qin L. Effect of celecoxib plus standard chemotherapy on cancer prognosis: A systematic review and meta-analysis Eur. J. Clin. Investig. 2023 53 e13973 10.1111/eci.13973 36807298 · DOI
  134. [135]Oplawski M. Dziobek K. Zmarzły N. Grabarek B.O. Kiełbasiński R. Kieszkowski P. Januszyk P. Talkowski K. Schweizer M. Kras P. Variances in the Level of COX-2 and iNOS in Different Grades of Endometrial Cancer Curr. Pharm. Biotechnol. 2020 21 52 59 10.2174/1389201020666190918104105 31533599 · DOI
  135. [136]Kosmas K. Mitropoulou G. Stamoulas M. Marouga A. Expression of cyclooxygenase-2 in imprint smears of endometrial carcinoma Diagn. Cytopathol. 2020 48 1086 1092 10.1002/dc.24481 32433831 · DOI
  136. [137]Lambropoulou M. Papadopoulos N. Tripsianis G. Alexiadis G. Pagonopoulou O. Kiziridou A. Liberis V. Kakolyris S. Chatzaki E. Co-expression of survivin, c-erbB2, and cyclooxygenase-2 (COX-2): Prognostic value and survival of endometrial cancer patients J. Cancer Res. Clin. Oncol. 2010 136 427 435 10.1007/s00432-009-0673-6 19756737 PMC11828219 · DOI
  137. [138]Li M. Li M. Wei Y. Xu H. Prognostic and Clinical Significance of Cyclooxygenase-2 Overexpression in Endometrial Cancer: A Meta-Analysis Front. Oncol. 2020 10 1202 10.3389/fonc.2020.01202 32903705 PMC7438859 · DOI
  138. [139]Hasegawa K. Ohashi Y. Ishikawa K. Yasue A. Kato R. Achiwa Y. Nishio E. Udagawa Y. Expression of cyclooxygenase-2 in uterine endometrial cancer and anti-tumor effects of a selective COX-2 inhibitor Int. J. Oncol. 2005 26 1419 1428 10.3892/ijo.26.5.1419 15809736 · DOI
  139. [140]Ma X. Hui Y. Lin L. Wu Y. Zhang X. Liu P. Clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues Pak. J. Med. Sci. 2015 31 280 284 10.12669/pjms.312.6604 26101475 PMC4476326 · DOI
  140. [141]Cai S. Zhang Y.X. Han K. Ding Y.Q. Expressions and clinical significance of COX-2, VEGF-C, and EFGR in endometrial carcinoma Arch. Gynecol. Obstet. 2017 296 93 98 10.1007/s00404-017-4386-9 28474124 · DOI
  141. [142]Hasegawa K. Ishikawa K. Kawai S. Torii Y. Kawamura K. Kato R. Tsukada K. Udagawa Y. Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor Oncol. Rep. 2013 30 2937 2944 10.3892/or.2013.2790 24100466 · DOI
  142. [143]Fowler J.M. Ramirez N. Cohn D.E. Kelbick N. Pavelka J. Ben-Shachar I. Morrison C. Correlation of cyclooxygenase-2 (COX-2) and aromatase expression in human endometrial cancer: Tissue microarray analysis Am. J. Obstet. Gynecol. 2005 192 1262 1273 1262–1271; discussion 1271–1273 10.1016/j.ajog.2005.01.009 15846217 · DOI
  143. [144]Tamura M. Sebastian S. Yang S. Gurates B. Fang Z. Okamura K. Bulun S.E. Induction of cyclooxygenase-2 in human endometrial stromal cells by malignant endometrial epithelial cells: Evidence for the involvement of extracellularly regulated kinases and CCAAT/enhancer binding proteins J. Mol. Endocrinol. 2003 31 95 104 10.1677/jme.0.0310095 12914528 · DOI
  144. [145]Weber A. Casini A. Heine A. Kuhn D. Supuran C.T. Scozzafava A. Klebe G. Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-selective celecoxib: New pharmacological opportunities due to related binding site recognition J. Med. Chem. 2004 47 550 557 10.1021/jm030912m 14736236 · DOI
  145. [146]Knudsen J.F. Carlsson U. Hammarström P. Sokol G.H. Cantilena L.R. The cyclooxygenase-2 inhibitor celecoxib is a potent inhibitor of human carbonic anhydrase II Inflammation 2004 28 285 290 10.1007/s10753-004-6052-1 16134002 · DOI
  146. [147]Sethi K.K. Vullo D. Verma S.M. Tanç M. Carta F. Supuran C.T. Carbonic anhydrase inhibitors: Synthesis and inhibition of the human carbonic anhydrase isoforms I, II, VII, IX and XII with benzene sulfonamides incorporating 4,5,6,7-tetrabromophthalimide moiety Bioorg. Med. Chem. 2013 21 5973 5982 10.1016/j.bmc.2013.07.044 23965175 · DOI
  147. [148]Erkanli S. Bolat F. Kayaselcuk F. Demirhan B. Kuscu E. COX-2 and survivin are overexpressed and positively correlated in endometrial carcinoma Gynecol. Oncol. 2007 104 320 325 10.1016/j.ygyno.2006.08.044 17030351 · DOI
  148. [149]Sadlecki P. Bodnar M. Grabiec M. Marszalek A. Walentowicz P. Sokup A. Zegarska J. Walentowicz-Sadlecka M. The role of Hypoxia-inducible factor-1 α, glucose transporter-1, (GLUT-1) and carbon anhydrase IX in endometrial cancer patients Biomed. Res. Int. 2014 2014 616850 10.1155/2014/616850 24745019 PMC3972900 · DOI
  149. [150]Hynninen P. Parkkila S. Huhtala H. Pastorekova S. Pastorek J. Waheed A. Sly W.S. Tomas E. Carbonic anhydrase isozymes II, IX, and XII in uterine tumors APMIS 2012 120 117 129 10.1111/j.1600-0463.2011.02820.x 22229267 · DOI
  150. [151]Swietach P. Vaughan-Jones R.D. Harris A.L. Regulation of tumor pH and the role of carbonic anhydrase 9 Cancer Metastasis Rev. 2007 26 299 310 10.1007/s10555-007-9064-0 17415526 · DOI · Paper page
  151. [152]Huang R. Yu J. Zhang B. Li X. Liu H. Wang Y. Emerging COX-2 inhibitors based nanotherapeutics for cancer diagnosis and treatment Biomaterials 2025 315 122954 10.1016/j.biomaterials.2024.122954 39549439 · DOI
  152. [153]Chiche J. Ilc K. Laferrière J. Trottier E. Dayan F. Mazure N.M. Brahimi-Horn M.C. Pouysségur J. Hypoxia-inducible carbonic anhydrase IX and XII promote tumor cell growth by counteracting acidosis through the regulation of the intracellular pH Cancer Res. 2009 69 358 368 10.1158/0008-5472.CAN-08-2470 19118021 · DOI
  153. [154]McDonald P.C. Dedhar S. Carbonic anhydrase IX (CAIX) as a mediator of hypoxia-induced stress response in cancer cells Subc. Biochem. 2014 75 255 269 10.1007/978-94-007-7359-2_13 24146383 · DOI
  154. [155]Benej M. Pastorekova S. Pastorek J. Carbonic anhydrase IX: Regulation and role in cancer Subc. Biochem. 2014 75 199 219 10.1007/978-94-007-7359-2_11 24146381 · DOI
  155. [156]Doyen J. Parks S.K. Marcié S. Pouysségur J. Chiche J. Knock-down of hypoxia-induced carbonic anhydrases IX and XII radiosensitizes tumor cells by increasing intracellular acidosis Front. Oncol. 2013 2 199 10.3389/fonc.2012.00199 23316475 PMC3539669 · DOI
  156. [157]Tafreshi N.K. Lloyd M.C. Bui M.M. Gillies R.J. Morse D.L. Carbonic anhydrase IX as an imaging and therapeutic target for tumors and metastases Subc. Biochem. 2014 75 221 254 10.1007/978-94-007-7359-2_12 PMC4282494 24146382 · DOI
  157. [158]Robertson N. Potter C. Harris A.L. Role of carbonic anhydrase IX in human tumor cell growth, survival, and invasion Cancer Res. 2004 64 6160 6165 10.1158/0008-5472.CAN-03-2224 15342400 · DOI
  158. [159]Chen F. Licarete E. Wu X. Petrusca D. Maguire C. Jacobsen M. Colter A. Sandusky G.E. Czader M. Capitano M.L. Pharmacological inhibition of Carbonic Anhydrase IX and XII to enhance targeting of acute myeloid leukaemia cells under hypoxic conditions J. Cell Mol. Med. 2021 25 11039 11052 10.1111/jcmm.17027 34791807 PMC8650039 · DOI
  159. [160]Alyaqubi K.J. Dosh R.H. Al-Fatlawi R.B. Al-Rehemi S.M. Hadi N.R. Gene expression of carbonic anhydrase 9 (CA9) in de novo acute leukemia as a predictive marker for prognosis J. Med. Life 2022 15 1158 1163 10.25122/jml-2021-0212 36415514 PMC9635246 · DOI
  160. [161]Hussain S.A. Palmer D.H. Ganesan R. Hiller L. Gregory J. Murray P.G. Pastorek J. Young L. James N.D. Carbonic anhydrase IX, a marker of hypoxia: Correlation with clinical outcome in transitional cell carcinoma of the bladder Oncol. Rep. 2004 11 1005 1010 10.3892/or.11.5.1005 15069539 · DOI
  161. [162]Urquidi V. Goodison S. Kim J. Chang M. Dai Y. Rosser C.J. Vascular endothelial growth factor, carbonic anhydrase 9, and angiogenin as urinary biomarkers for bladder cancer detection Urology 2012 79 1185.e1 1185.e6 10.1016/j.urology.2012.01.016 PMC3341520 22386755 · DOI
  162. [163]De Martino M. Lucca I. Mbeutcha A. Wiener H.G. Haitel A. Susani M. Shariat S.F. Klatte T. Carbonic anhydrase IX as a diagnostic urinary marker for urothelial bladder cancer Eur. Urol. 2015 68 552 554 10.1016/j.eururo.2015.06.015 26138037 · DOI
  163. [164]Malentacchi F. Vinci S. Della Melina A. Kuncova J. Villari D. Giannarini G. Nesi G. Selli C. Orlando C. Splicing variants of carbonic anhydrase IX in bladder cancer and urine sediments Urol. Oncol. 2012 30 278 284 10.1016/j.urolonc.2010.05.009 20875751 · DOI
  164. [165]Klatte T. Seligson D.B. Rao J.Y. Yu H. de Martino M. Kawaoka K. Wong S.G. Belldegrun A.S. Pantuck A.J. Carbonic anhydrase IX in bladder cancer: A diagnostic, prognostic, and therapeutic molecular marker Cancer 2009 115 1448 1458 10.1002/cncr.24163 19195047 · DOI
  165. [166]Xiang A.P. Chen X.N. Xu P.F. Shao S.H. Shen Y.F. Expression and prognostic value of carbonic anhydrase IX (CA-IX) in bladder urothelial carcinoma BMC Urol. 2022 22 120 10.1186/s12894-022-01074-9 35922856 PMC9347144 · DOI
  166. [167]Shamis S.A.K. Edwards J. McMillan D.C. The relationship between carbonic anhydrase IX (CAIX) and patient survival in breast cancer: Systematic review and meta-analysis Diagn. Pathol. 2023 18 46 10.1186/s13000-023-01325-9 37061698 PMC10105416 · DOI
  167. [168]Ochi F. Shiozaki A. Ichikawa D. Fujiwara H. Nakashima S. Takemoto K. Kosuga T. Konishi H. Komatsu S. Okamoto K. Carbonic Anhydrase XII as an Independent Prognostic Factor in Advanced Esophageal Squamous Cell Carcinoma J. Cancer 2015 6 922 929 10.7150/jca.11269 26316888 PMC4543752 · DOI
  168. [169]Driessen A. Landuyt W. Pastorekova S. Moons J. Goethals L. Haustermans K. Nafteux P. Penninckx F. Geboes K. Lerut T. Expression of carbonic anhydrase IX (CA IX), a hypoxia-related protein, rather than vascular-endothelial growth factor (VEGF), a pro-angiogenic factor, correlates with an extremely poor prognosis in esophageal and gastric adenocarcinomas Ann. Surg. 2006 243 334 340 10.1097/01.sla.0000201452.09591.f3 16495697 PMC1448952 · DOI
  169. [170]Fidan E. Mentese A. Ozdemir F. Deger O. Kavgaci H. Caner Karahan S. Aydin F. Diagnostic and prognostic significance of CA IX and suPAR in gastric cancer Med. Oncol. 2013 30 540 10.1007/s12032-013-0540-9 23512428 · DOI
  170. [171]Li G. Chen T.W. Nickel A.C. Muhammad S. Steiger H.J. Tzaridis T. Hänggi D. Zeidler R. Zhang W. Kahlert U.D. Carbonic Anhydrase XII is a Clinically Significant, Molecular Tumor-Subtype Specific Therapeutic Target in Glioma with the Potential to Combat Invasion of Brain Tumor Cells OncoTargets Ther. 2021 14 1707 1718 10.2147/OTT.S300623 PMC7939492 33692626 · DOI
  171. [172]Gu X.F. Shi C.B. Zhao W. Prognostic value of carbonic anhydrase XII (CA XII) overexpression in hepatocellular carcinoma Int. J. Clin. Exp. Pathol. 2019 12 2173 2183 31934040 PMC6949632
  172. [173]Méhes G. Matolay O. Beke L. Czenke M. Jóna Á. Miltényi Z. Illés Á. Bedekovics J. Hypoxia-related carbonic anhydrase IX expression is associated with unfavourable response to first-line therapy in classical Hodgkin’s lymphoma Histopathology 2019 74 699 708 10.1111/his.13808 30636023 · DOI
  173. [174]Kwon O.J. Park J.J. Ko G.H. Seo J.H. Jeong B.K. Kang K.M. Woo S.H. Kim J.P. Hwa J.S. Carey T.E. HIF-1α and CA-IX as predictors of locoregional control for determining the optimal treatment modality for early-stage laryngeal carcinoma Head Neck 2015 37 505 510 10.1002/hed.23620 24677746 · DOI
  174. [175]Hu C. Wang H. Lin L. Sun X. Wang D. Association between carbonic anhydrase 9 expression and poor prognosis in sinonasal squamous cell carcinoma Ann. Diagn. Pathol. 2020 49 151643 10.1016/j.anndiagpath.2020.151643 33126151 · DOI
  175. [176]Hui E.P. Chan A.T. Pezzella F. Turley H. To K.F. Poon T.C. Zee B. Mo F. Teo P.M. Huang D.P. Coexpression of hypoxia-inducible factors 1alpha and 2alpha, carbonic anhydrase IX, and vascular endothelial growth factor in nasopharyngeal carcinoma and relationship to survival Clin. Cancer Res. 2002 8 2595 2604 12171890
  176. [177]Fecikova S. Csaderova L. Belvoncikova P. Puzderova B. Bernatova K. Talac T. Pastorek J. Barathova M. Can hypoxia marker carbonic anhydrase IX serve as a potential new diagnostic marker and therapeutic target of non-small cell lung cancer? Neoplasma 2024 71 123 142 10.4149/neo_2024_231219N652 38766851 · DOI
  177. [178]Eckert A.W. Horter S. Bethmann D. Kotrba J. Kaune T. Rot S. Bache M. Bilkenroth U. Reich W. Greither T. Investigation of the Prognostic Role of Carbonic Anhydrase 9 (CAIX) of the Cellular mRNA/Protein Level or Soluble CAIX Protein in Patients with Oral Squamous Cell Carcinoma Int. J. Mol. Sci. 2019 20 375 10.3390/ijms20020375 30654595 PMC6359351 · DOI
  178. [179]Nazon C. Pierrevelcin M. Willaume T. Lhermitte B. Weingertner N. Marco A.D. Bund L. Vincent F. Bierry G. Gomez-Brouchet A. Together Intra-Tumor Hypoxia and Macrophagic Immunity Are Driven Worst Outcome in Pediatric High-Grade Osteosarcomas Cancers 2022 14 1482 10.3390/cancers14061482 35326631 PMC8945994 · DOI
  179. [180]Li Y. Dong M. Sheng W. Huang L. Roles of Carbonic Anhydrase IX in Development of Pancreatic Cancer Pathol. Oncol. Res. 2016 22 277 286 10.1007/s12253-015-9935-6 26224207 · DOI
  180. [181]Schmidt J. Oppermann E. Blaheta R.A. Schreckenbach T. Lunger I. Rieger M.A. Bechstein W.O. Holzer K. Malkomes P. Carbonic-anhydrase IX expression is increased in thyroid cancer tissue and represents a potential therapeutic target to eradicate thyroid tumor-initiating cells Mol. Cell. Endocrinol. 2021 535 111382 10.1016/j.mce.2021.111382 34216643 · DOI
  181. [182]Mujumdar P. Kopecka J. Bua S. Supuran C.T. Riganti C. Poulsen S.A. Carbonic Anhydrase XII Inhibitors Overcome Temozolomide Resistance in Glioblastoma J. Med. Chem. 2019 62 4174 4192 10.1021/acs.jmedchem.9b00282 30925064 · DOI
  182. [183]Salaroglio I.C. Mujumdar P. Annovazzi L. Kopecka J. Mellai M. Schiffer D. Poulsen S.A. Riganti C. Carbonic Anhydrase XII Inhibitors Overcome P-Glycoprotein-Mediated Resistance to Temozolomide in Glioblastoma Mol. Cancer Ther. 2018 17 2598 2609 10.1158/1535-7163.MCT-18-0533 30254183 · DOI
  183. [184]Azadehrah M. Vosoogh S. Azadehrah M. The roles and therapeutic applications of cytokines in endometrial cancer J. Reprod. Immunol. 2022 152 103652 10.1016/j.jri.2022.103652 35753146 · DOI
  184. [185]Ma J. Liu D. Mao X. Huang L. Ren Y. Xu X. Huang X. Deng C. Shi F. Sun P. Enhanced Diagnostic Efficiency of Endometrial Carcinogenesis and Progression in Women with Abnormal Uterine Bleeding through Peripheral Blood Cytokine Testing: A Multicenter Retrospective Cohort Study Int. J. Med. Sci. 2024 21 601 611 10.7150/ijms.91506 38464838 PMC10920852 · DOI
  185. [186]Lu W. He F. Lin Z. Liu S. Tang L. Huang Y. Hu Z. Dysbiosis of the endometrial microbiota and its association with inflammatory cytokines in endometrial cancer Int. J. Cancer 2021 148 1708 1716 10.1002/ijc.33428 33285000 · DOI
  186. [187]Yan Y. Guo T.M. Zhu C. Effects of nonsteroidal anti-inflammatory drugs on serum proinflammatory cytokines in the treatment of ankylosing spondylitis Biochem. Cell Biol. 2018 96 450 456 10.1139/bcb-2017-0267 29324184 · DOI
  187. [188]Huang Z. Ma X. Jia X. Wang R. Liu L. Zhang M. Wan X. Tang C. Huang L. Prevention of Severe Acute Pancreatitis With Cyclooxygenase-2 Inhibitors: A Randomized Controlled Clinical Trial Am. J. Gastroenterol. 2020 115 473 480 10.14309/ajg.0000000000000529 32142484 PMC7060052 · DOI
  188. [189]Abbasi S.H. Hosseini F. Modabbernia A. Ashrafi M. Akhondzadeh S. Effect of celecoxib add-on treatment on symptoms and serum IL-6 concentrations in patients with major depressive disorder: Randomized double-blind placebo-controlled study J. Affect. Disord. 2012 141 308 314 10.1016/j.jad.2012.03.033 22516310 · DOI
  189. [190]Mao J.T. Roth M.D. Fishbein M.C. Aberle D.R. Zhang Z.F. Rao J.Y. Tashkin D.P. Goodglick L. Holmes E.C. Cameron R.B. Lung cancer chemoprevention with celecoxib in former smokers Cancer Prev. Res. 2011 4 984 993 10.1158/1940-6207.CAPR-11-0078 PMC3153413 21733822 · DOI
  190. [191]Mets T. Bautmans I. Njemini R. Lambert M. Demanet C. The influence of celecoxib on muscle fatigue resistance and mobility in elderly patients with inflammation Am. J. Geriatr. Pharmacother. 2004 2 230 238 10.1016/j.amjopharm.2004.12.007 15903281 · DOI
  191. [192]Bianchi M. Broggini M. Balzarini P. Franchi S. Sacerdote P. Effects of nimesulide on pain and on synovial fluid concentrations of substance P, interleukin-6 and interleukin-8 in patients with knee osteoarthritis: Comparison with celecoxib Int. J. Clin. Pract. 2007 61 1270 1277 10.1111/j.1742-1241.2007.01453.x 17590218 · DOI
  192. [193]Theodoridou A. Gika H. Diza E. Garyfallos A. Settas L. In vivo study of pro-inflammatory cytokine changes in serum and synovial fluid during treatment with celecoxib and etoricoxib and correlation with VAS pain change and synovial membrane penetration index in patients with inflammatory arthritis Mediterr. J. Rheumatol. 2017 28 33 40 10.31138/mjr.28.1.33 32185252 PMC7045925 · DOI
  193. [194]Kaur S. Bansal Y. Kumar R. Bansal G. A panoramic review of IL-6, Structure, pathophysiological roles and inhibitors Bioorg. Med. Chem. 2020 28 115327 10.1016/j.bmc.2020.115327 31992476 · DOI
  194. [195]Mauer J. Denson J.L. Brüning J.C. Versatile functions for IL-6 in metabolism and cancer Trends Immunol. 2015 36 92 101 10.1016/j.it.2014.12.008 25616716 · DOI
  195. [196]Che Q. Xiao X. Liu M. Lu Y. Dong X. Liu S. IL-6 promotes endometrial cancer cells invasion and migration through signal transducers and activators of transcription 3 signaling pathway Pathol. Res. Pract. 2019 215 152392 10.1016/j.prp.2019.03.020 30922625 · DOI
  196. [197]Li X. Li H. Pei X. Zhou Y. Wei Z. CCDC68 Upregulation by IL-6 Promotes Endometrial Carcinoma Progression J. Interferon Cytokine Res. 2021 41 12 19 10.1089/jir.2020.0193 33471616 · DOI
  197. [198]Chu Y. Wang Y. Peng W. Xu L. Liu M. Li J. Hu X. Li Y. Zuo J. Ye Y. STAT3 activation by IL-6 from adipose-derived stem cells promotes endometrial carcinoma proliferation and metastasis Biochem. Biophys. Res. Commun. 2018 500 626 631 10.1016/j.bbrc.2018.04.121 29684351 · DOI
  198. [199]So K.A. Min K.J. Hong J.H. Lee J.K. Interleukin-6 expression by interactions between gynecologic cancer cells and human mesenchymal stem cells promotes epithelial-mesenchymal transition Int. J. Oncol. 2015 47 1451 1459 10.3892/ijo.2015.3122 26316317 · DOI
  199. [200]Slater M. Cooper M. Murphy C.R. Human growth hormone and interleukin-6 are upregulated in endometriosis and endometrioid adenocarcinoma Acta Histochem. 2006 108 13 18 10.1016/j.acthis.2006.01.004 16564564 · DOI
  200. [201]Che Q. Liu B.Y. Liao Y. Zhang H.J. Yang T.T. He Y.Y. Xia Y.H. Lu W. He X.Y. Chen Z. Activation of a positive feedback loop involving IL-6 and aromatase promotes intratumoral 17β-estradiol biosynthesis in endometrial carcinoma microenvironment Int. J. Cancer 2014 135 282 294 10.1002/ijc.28679 24347287 · DOI

200 of 303 shown

Cited by

Sorted by citations

Authors
Kast, R. E.
Affiliations
IIAIGC Study Center, Burlington, VT 05408, USA
Corresponding author
Kast, Richard E.
ORCID
Kast, Richard E.
Venue
Current Issues in Molecular Biology
Publisher
MDPI AG
Published
2025-02-26
Volume
47
Issue
3
Pages
153
ISSN
  • 1467-3037 (ISSN-L)
  • 1467-3045
DOI
10.3390/cimb47030153
PMC
PMC11941490
OpenAlex
W4407954404
Cited by
5
References
5
Citations by year
2026: 4 · 2025: 1
FWCI
5.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Issues in Molecular Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
Keywords
metastatic endometrial cancer, drug repurposing, alendronate, celecoxib, itraconazole, ramelteon, simvastatin, combination therapy, cancer growth inhibition, osteoporosis treatment, antifungal agents, cholesterol-lowering drugs, sleep aids

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review