{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T01:36:49Z","timestamp":1778290609880,"version":"3.51.4"},"reference-count":86,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T00:00:00Z","timestamp":1708300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T00:00:00Z","timestamp":1708300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Taizhou Municipal Science and Technology Bureau","award":["21ywb112"],"award-info":[{"award-number":["21ywb112"]}]},{"name":"The Wenling Social Development Science and Technology Project","award":["2021S00003"],"award-info":[{"award-number":["2021S00003"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Orthop Surg Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Patients are typically diagnosed with both hypertension and fibrosarcoma. Medical oncologists must prescribe suitable anti-hypertensive medications while considering anti-tumor drugs. Recently, immunotherapy has become prominent in cancer treatment. Nonetheless, it is unknown what role anti-hypertensive medications will play in immunotherapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We examined the effects of six first-line anti-hypertensive medications on programmed cell death protein 1 antibody (PD1ab) in tumor treatment using a mouse model of subcutaneous fibrosarcoma. The drugs examined were verapamil, losartan, furosemide, spironolactone, captopril, and hydrochlorothiazide (HCTZ). The infiltration of CD8<jats:sup>+<\/jats:sup> T cells was examined by immunohistochemistry. Additionally, several in vitro and in vivo assays were used to study the effects of HCTZ on human fibrosarcoma cancer cells to explore its mechanism.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Verapamil suppressed tumor growth and showed an improved effect on the tumor inhibition of PD1ab. Captopril did not affect tumor growth but brought an unexpected benefit to PD1ab treatment. In contrast, spironolactone and\u00a0furosemide showed no effect on tumor growth but had an offset effect on the PD1ab therapy. Consequently, the survival time of mice was also significantly reduced. Notably, losartan and HCTZ, especially HCTZ, promoted tumor growth and weakened the effect of PD1ab treatment. Consistent results were observed in vivo and in vitro using the human fibrosarcoma cell line HT1080. We determined that the Solute Carrier Family 12 Member 3 (SLC12A3), a known target of HCTZ, may be the principal factor underlying its effect-enhancing properties through mechanism studies employing The Cancer Genome Atlas (TCGA) data and in vivo and in vitro assays.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Verapamil and captopril potentiated the anti-tumor effect of PD1ab, whereas spironolactone and\u00a0furosemide weakened the effect of PD1ab on tumor inhibition. Alarmingly, losartan and HCTZ promoted tumor growth and impaired the effect of PD1ab. Furthermore, we preliminarily found that HCTZ may promote tumor progression through SLC12A3. Based on this study, futher mechanism researches and clinical trials should be conducted in the future.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13018-024-04627-w","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T10:08:04Z","timestamp":1708337284000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Several first-line anti-hypertensives act on fibrosarcoma progression and PD1ab blockade therapy"],"prefix":"10.1186","volume":"19","author":[{"given":"Jianwen","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaoxiong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinhao","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoyun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minjie","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Binbo","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,19]]},"reference":[{"issue":"2","key":"4627_CR1","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s13277-014-2672-8","volume":"36","author":"O Meral","year":"2015","unstructured":"Meral O, Uysal H. Comparative proteomic analysis of fibrosarcoma and skin fibroblast cell lines. Tumour Biol. 2015;36(2):561\u20137.","journal-title":"Tumour Biol"},{"issue":"22","key":"4627_CR2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.022479","volume":"10","author":"H Kaneko","year":"2021","unstructured":"Kaneko H, et al. Untreated hypertension and subsequent incidence of colorectal cancer: analysis of a nationwide epidemiological database. J Am Heart Assoc. 2021;10(22): e022479.","journal-title":"J Am Heart Assoc"},{"issue":"6","key":"4627_CR3","first-page":"944","volume":"50","author":"H Wang","year":"2021","unstructured":"Wang H, et al. Association between hypertension and oral cancer prognosis in non-smoking and non-drinking women. Wei Sheng Yan Jiu. 2021;50(6):944\u201351.","journal-title":"Wei Sheng Yan Jiu"},{"issue":"17","key":"4627_CR4","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.1111\/1759-7714.14076","volume":"12","author":"J Shi","year":"2021","unstructured":"Shi J, et al. Occurrence of hypertension during third-line anlotinib is associated with progression-free survival in patients with squamous cell lung cancer (SCC): a post hoc analysis of the ALTER0303 trial. Thorac Cancer. 2021;12(17):2345\u201351.","journal-title":"Thorac Cancer"},{"issue":"1","key":"4627_CR5","doi-asserted-by":"publisher","first-page":"10291","DOI":"10.1038\/s41598-020-67329-3","volume":"10","author":"JH Seo","year":"2020","unstructured":"Seo JH, et al. Hypertension is associated with oral, laryngeal, and esophageal cancer: a nationwide population-based study. Sci Rep. 2020;10(1):10291.","journal-title":"Sci Rep"},{"issue":"13","key":"4627_CR6","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1042\/CS20200307","volume":"135","author":"A Sionakidis","year":"2021","unstructured":"Sionakidis A, McCallum L, Padmanabhan S. Unravelling the tangled web of hypertension and cancer. Clin Sci (Lond). 2021;135(13):1609\u201325.","journal-title":"Clin Sci (Lond)"},{"key":"4627_CR7","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.921676","volume":"26","author":"X Zeng","year":"2020","unstructured":"Zeng X, et al. Influence of hypertension on the survival of non-small cell lung cancer patients with type 2 diabetes mellitus. Med Sci Monit. 2020;26: e921676.","journal-title":"Med Sci Monit"},{"issue":"17","key":"4627_CR8","first-page":"5508","volume":"22","author":"GF Fan","year":"2018","unstructured":"Fan GF, et al. The clinical observation of verapamil in combination with interventional chemotherapy in advanced gastric cancer. Eur Rev Med Pharmacol Sci. 2018;22(17):5508\u201318.","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"4627_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2022.115887","volume":"437","author":"SK Nandi","year":"2022","unstructured":"Nandi SK, et al. Deregulation of the CD44-NANOG-MDR1 associated chemoresistance pathways of breast cancer stem cells potentiates the anti-cancer effect of Kaempferol in synergism with Verapamil. Toxicol Appl Pharmacol. 2022;437: 115887.","journal-title":"Toxicol Appl Pharmacol"},{"issue":"9026","key":"4627_CR10","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/S0140-6736(96)04277-8","volume":"348","author":"M Pahor","year":"1996","unstructured":"Pahor M, et al. Calcium-channel blockade and incidence of cancer in aged populations. Lancet. 1996;348(9026):493\u20137.","journal-title":"Lancet"},{"issue":"5","key":"4627_CR11","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1177\/1060028018814684","volume":"53","author":"V Rotshild","year":"2019","unstructured":"Rotshild V, et al. Calcium channel blockers and the risk for lung cancer: a population-based nested case-control study. Ann Pharmacother. 2019;53(5):445\u201352.","journal-title":"Ann Pharmacother"},{"issue":"4","key":"4627_CR12","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s10552-017-0857-3","volume":"28","author":"JS Colt","year":"2017","unstructured":"Colt JS, et al. Antihypertensive medication use and risk of renal cell carcinoma. Cancer Causes Control. 2017;28(4):289\u201397.","journal-title":"Cancer Causes Control"},{"issue":"4","key":"4627_CR13","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1254\/jjp.87.318","volume":"87","author":"K Ishihara","year":"2001","unstructured":"Ishihara K, et al. A potential role of bradykinin in angiogenesis and growth of S-180 mouse tumors. Jpn J Pharmacol. 2001;87(4):318\u201326.","journal-title":"Jpn J Pharmacol"},{"issue":"13","key":"4627_CR14","doi-asserted-by":"publisher","first-page":"4095","DOI":"10.1158\/1078-0432.CCR-05-2489","volume":"12","author":"PJ Wysocki","year":"2006","unstructured":"Wysocki PJ, et al. Captopril, an angiotensin-converting enzyme inhibitor, promotes growth of immunogenic tumors in mice. Clin Cancer Res. 2006;12(13):4095\u2013102.","journal-title":"Clin Cancer Res"},{"issue":"4","key":"4627_CR15","first-page":"1967","volume":"18","author":"RI Shebl","year":"2019","unstructured":"Shebl RI. Anti-cancer potential of captopril and botulinum toxin type-A and associated p53 gene apototic stimulating activity. Iran J Pharm Res. 2019;18(4):1967\u201377.","journal-title":"Iran J Pharm Res"},{"issue":"4","key":"4627_CR16","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1111\/bcp.14568","volume":"87","author":"BM Hiebert","year":"2021","unstructured":"Hiebert BM, et al. Impact of spironolactone exposure on prostate cancer incidence amongst men with heart failure: a Pharmacoepidemiological study. Br J Clin Pharmacol. 2021;87(4):1801\u201313.","journal-title":"Br J Clin Pharmacol"},{"issue":"17","key":"4627_CR17","doi-asserted-by":"publisher","first-page":"3103","DOI":"10.1038\/s41388-018-0654-9","volume":"38","author":"A Gold","year":"2019","unstructured":"Gold A, et al. Spironolactone inhibits the growth of cancer stem cells by impairing DNA damage response. Oncogene. 2019;38(17):3103\u201318.","journal-title":"Oncogene"},{"issue":"1","key":"4627_CR18","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s10549-018-4996-3","volume":"174","author":"RN Rozner","year":"2019","unstructured":"Rozner RN, et al. Safety of 5\u03b1-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies. Breast Cancer Res Treat. 2019;174(1):15\u201326.","journal-title":"Breast Cancer Res Treat"},{"issue":"7","key":"4627_CR19","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/S1470-2045(10)70106-6","volume":"11","author":"I Sipahi","year":"2010","unstructured":"Sipahi I, et al. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. 2010;11(7):627\u201336.","journal-title":"Lancet Oncol"},{"issue":"5","key":"4627_CR20","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1016\/j.ijcard.2012.05.096","volume":"167","author":"KL Wang","year":"2013","unstructured":"Wang KL, et al. Long-term use of angiotensin II receptor blockers and risk of cancer: a population-based cohort analysis. Int J Cardiol. 2013;167(5):2162\u20136.","journal-title":"Int J Cardiol"},{"issue":"2","key":"4627_CR21","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s40264-020-01015-1","volume":"44","author":"J Rouette","year":"2021","unstructured":"Rouette J, et al. Use of hydrochlorothiazide and risk of melanoma and nonmelanoma skin cancer. Drug Saf. 2021;44(2):245\u201354.","journal-title":"Drug Saf"},{"issue":"4","key":"4627_CR22","doi-asserted-by":"publisher","first-page":"F838","DOI":"10.1152\/ajprenal.00159.2009","volume":"297","author":"G Gamba","year":"2009","unstructured":"Gamba G. The thiazide-sensitive Na+-Cl- cotransporter: molecular biology, functional properties, and regulation by WNKs. Am J Physiol Renal Physiol. 2009;297(4):F838\u201348.","journal-title":"Am J Physiol Renal Physiol"},{"key":"4627_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jpba.2018.09.009","volume":"162","author":"F Balaei","year":"2019","unstructured":"Balaei F, Ghobadi S. Hydrochlorothiazide binding to human serum albumin induces some compactness in the molecular structure of the protein: a multi-spectroscopic and computational study. J Pharm Biomed Anal. 2019;162:1\u20138.","journal-title":"J Pharm Biomed Anal"},{"issue":"1","key":"4627_CR24","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1681\/ASN.2005090966","volume":"18","author":"M Hasegawa","year":"2007","unstructured":"Hasegawa M, et al. Multidrug resistance-associated protein 4 is involved in the urinary excretion of hydrochlorothiazide and furosemide. J Am Soc Nephrol. 2007;18(1):37\u201345.","journal-title":"J Am Soc Nephrol"},{"key":"4627_CR25","doi-asserted-by":"publisher","first-page":"561","DOI":"10.3389\/fphar.2017.00561","volume":"8","author":"HO Alsaab","year":"2017","unstructured":"Alsaab HO, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol. 2017;8:561.","journal-title":"Front Pharmacol"},{"issue":"2","key":"4627_CR26","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1002\/ijc.21775","volume":"119","author":"C Blank","year":"2006","unstructured":"Blank C, et al. Blockade of PD-L1 (B7\u2013H1) augments human tumor-specific T cell responses in vitro. Int J Cancer. 2006;119(2):317\u201327.","journal-title":"Int J Cancer"},{"key":"4627_CR27","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/978-981-15-3266-5_3","volume":"1248","author":"L Ai","year":"2020","unstructured":"Ai L, Xu A, Xu J. Roles of PD-1\/PD-L1 pathway: signaling, cancer, and beyond. Adv Exp Med Biol. 2020;1248:33\u201359.","journal-title":"Adv Exp Med Biol"},{"issue":"5","key":"4627_CR28","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.cllc.2017.02.001","volume":"18","author":"PM Ellis","year":"2017","unstructured":"Ellis PM, Vella ET, Ung YC. Immune checkpoint inhibitors for patients with advanced non-small-cell lung cancer: a systematic review. Clin Lung Cancer. 2017;18(5):444.","journal-title":"Clin Lung Cancer"},{"key":"4627_CR29","unstructured":"Marte F, Sankar P, Cassagnol M. Captopril. In: StatPearls. 2022;StatPearls Publishing"},{"key":"4627_CR30","unstructured":"Copyright \u00a9 2022, StatPearls Publishing LLC.: Treasure Island (FL)."},{"key":"4627_CR31","unstructured":"Mulla, S, Siddiqui WJ. Losartan. In: StatPearls. 2022;StatPearls Publishing Copyright \u00a9 2022, StatPearls Publishing LLC.: Treasure Island (FL)."},{"key":"4627_CR32","unstructured":"Khan TM, Patel R, Siddiqui AH. Furosemide. In StatPearls. 2022;StatPearls Publishing Copyright \u00a9 2022, StatPearls Publishing LLC.: Treasure Island (FL)."},{"key":"4627_CR33","unstructured":"Patibandla S, Heaton J, Kyaw H. Spironolactone. In StatPearls. 2022;StatPearls Publishing Copyright \u00a9 2022, StatPearls Publishing LLC.: Treasure Island (FL)."},{"key":"4627_CR34","unstructured":"Herman LL, Bashir K. Hydrochlorothiazide. In: StatPearls. 2022;StatPearls Publishing."},{"key":"4627_CR35","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.799224","volume":"13","author":"N Li","year":"2022","unstructured":"Li N, Gu HF. Genetic and biological effects of SLC12A3, a sodium-chloride cotransporter, in gitelman syndrome and diabetic kidney disease. Front Genet. 2022;13: 799224.","journal-title":"Front Genet"},{"issue":"4","key":"4627_CR36","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1007\/s00280-010-1385-y","volume":"67","author":"Y D\u00f6nmez","year":"2011","unstructured":"D\u00f6nmez Y, et al. Effect of MDR modulators verapamil and promethazine on gene expression levels of MDR1 and MRP1 in doxorubicin-resistant MCF-7 cells. Cancer Chemother Pharmacol. 2011;67(4):823\u20138.","journal-title":"Cancer Chemother Pharmacol"},{"issue":"1","key":"4627_CR37","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.bbrc.2019.05.189","volume":"516","author":"P Li","year":"2019","unstructured":"Li P, Zhong D, Gong PY. Synergistic effect of paclitaxel and verapamil to overcome multi-drug resistance in breast cancer cells. Biochem Biophys Res Commun. 2019;516(1):183\u20138.","journal-title":"Biochem Biophys Res Commun"},{"issue":"2","key":"4627_CR38","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.4976","volume":"35","author":"X Wang","year":"2021","unstructured":"Wang X, et al. Metabolomics analysis of multidrug resistance in colorectal cancer cell and multidrug resistance reversal effect of verapamil. Biomed Chromatogr. 2021;35(2): e4976.","journal-title":"Biomed Chromatogr"},{"issue":"9","key":"4627_CR39","doi-asserted-by":"publisher","first-page":"5412","DOI":"10.1245\/s10434-021-09647-y","volume":"28","author":"A Shiozaki","year":"2021","unstructured":"Shiozaki A, Katsurahara K, Otsuji E. ASO author reflections: amlodipine and verapamil, voltage-gated Ca(2+) channel inhibitors suppressed the growth of gastric cancer stem cells. Ann Surg Oncol. 2021;28(9):5412\u20133.","journal-title":"Ann Surg Oncol"},{"issue":"6","key":"4627_CR40","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1007\/s40264-018-0644-4","volume":"41","author":"V Rotshild","year":"2018","unstructured":"Rotshild V, et al. The risk for lung cancer incidence with calcium channel blockers: a systematic review and meta-analysis of observational studies. Drug Saf. 2018;41(6):555\u201364.","journal-title":"Drug Saf"},{"key":"4627_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.critrevonc.2017.12.003","volume":"122","author":"S Gandini","year":"2018","unstructured":"Gandini S, et al. Anti-hypertensive drugs and skin cancer risk: a review of the literature and meta-analysis. Crit Rev Oncol Hematol. 2018;122:1\u20139.","journal-title":"Crit Rev Oncol Hematol"},{"issue":"8","key":"4627_CR42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0159672","volume":"11","author":"I G\u00f3mez-Acebo","year":"2016","unstructured":"G\u00f3mez-Acebo I, et al. The use of antihypertensive medication and the risk of breast cancer in a case-control study in a Spanish population: the MCC-Spain study. PLoS ONE. 2016;11(8): e0159672.","journal-title":"PLoS ONE"},{"issue":"1","key":"4627_CR43","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12894-018-0318-7","volume":"18","author":"L Cao","year":"2018","unstructured":"Cao L, et al. Antihypertensive drugs use and the risk of prostate cancer: a meta-analysis of 21 observational studies. BMC Urol. 2018;18(1):17.","journal-title":"BMC Urol"},{"issue":"37","key":"4627_CR44","doi-asserted-by":"publisher","first-page":"62545","DOI":"10.18632\/oncotarget.19117","volume":"8","author":"H Ni","year":"2017","unstructured":"Ni H, et al. Antihypertensive drug use and breast cancer risk: a meta-analysis of observational studies. Oncotarget. 2017;8(37):62545\u201360.","journal-title":"Oncotarget"},{"issue":"1","key":"4627_CR45","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1080\/10641963.2017.1288736","volume":"40","author":"Y Zhao","year":"2018","unstructured":"Zhao Y, et al. Effect of antihypertensive drugs on breast cancer risk in female hypertensive patients: evidence from observational studies. Clin Exp Hypertens. 2018;40(1):22\u20137.","journal-title":"Clin Exp Hypertens"},{"issue":"4","key":"4627_CR46","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1097\/EDE.0000000000000483","volume":"27","author":"L Azoulay","year":"2016","unstructured":"Azoulay L, et al. Use of calcium channel blockers and risk of breast cancer: a population-based cohort study. Epidemiology. 2016;27(4):594\u2013601.","journal-title":"Epidemiology"},{"issue":"1","key":"4627_CR47","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S1470-2045(10)70260-6","volume":"12","author":"S Bangalore","year":"2011","unstructured":"Bangalore S, et al. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials. Lancet Oncol. 2011;12(1):65\u201382.","journal-title":"Lancet Oncol"},{"issue":"6","key":"4627_CR48","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1016\/j.canep.2013.09.001","volume":"37","author":"S Holmes","year":"2013","unstructured":"Holmes S, et al. Antihypertensive medications and survival in patients with cancer: a population-based retrospective cohort study. Cancer Epidemiol. 2013;37(6):881\u20135.","journal-title":"Cancer Epidemiol"},{"issue":"7","key":"4627_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/pharmaceutics14071478","volume":"14","author":"JI Veytia-Bucheli","year":"2022","unstructured":"Veytia-Bucheli JI, et al. The Ca(2+) channel blocker verapamil inhibits the in vitro activation and function of T lymphocytes: a 2022 reappraisal. Pharmaceutics. 2022;14(7):1.","journal-title":"Pharmaceutics"},{"issue":"4","key":"4627_CR50","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108327","volume":"33","author":"L Wu","year":"2020","unstructured":"Wu L, et al. Calcium channel blocker nifedipine suppresses colorectal cancer progression and immune escape by preventing NFAT2 nuclear translocation. Cell Rep. 2020;33(4): 108327.","journal-title":"Cell Rep"},{"issue":"7","key":"4627_CR51","doi-asserted-by":"publisher","first-page":"3544","DOI":"10.1021\/acsabm.2c00486","volume":"5","author":"X Chen","year":"2022","unstructured":"Chen X, et al. Cancer-associated fibroblast-targeted delivery of captopril to overcome penetration obstacles for enhanced pancreatic cancer therapy. ACS Appl Bio Mater. 2022;5(7):3544\u201353.","journal-title":"ACS Appl Bio Mater"},{"issue":"6","key":"4627_CR52","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1016\/j.ccell.2020.05.005","volume":"37","author":"Y Shen","year":"2020","unstructured":"Shen Y, et al. Reduction of liver metastasis stiffness improves response to bevacizumab in metastatic colorectal cancer. Cancer Cell. 2020;37(6):800.","journal-title":"Cancer Cell"},{"key":"4627_CR53","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1196\/annals.1414.011","volume":"1138","author":"S Attoub","year":"2008","unstructured":"Attoub S, et al. Captopril as a potential inhibitor of lung tumor growth and metastasis. Ann N Y Acad Sci. 2008;1138:65\u201372.","journal-title":"Ann N Y Acad Sci"},{"issue":"1","key":"4627_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2020.112114","volume":"394","author":"F Rasha","year":"2020","unstructured":"Rasha F, et al. Renin angiotensin system inhibition attenuates adipocyte-breast cancer cell interactions. Exp Cell Res. 2020;394(1): 112114.","journal-title":"Exp Cell Res"},{"issue":"9","key":"4627_CR55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms23095281","volume":"23","author":"GE Riddiough","year":"2022","unstructured":"Riddiough GE, et al. Captopril, a renin-angiotensin system inhibitor, attenuates tumour progression in the regenerating liver following partial hepatectomy. Int J Mol Sci. 2022;23(9):1.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"4627_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/jitc-2019-000487","volume":"8","author":"DL Vallejo Ardila","year":"2020","unstructured":"Vallejo Ardila DL, et al. Immunomodulatory effects of renin-angiotensin system inhibitors on T lymphocytes in mice with colorectal liver metastases. J Immunother Cancer. 2020;8(1):1.","journal-title":"J Immunother Cancer"},{"issue":"1","key":"4627_CR57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S1043-2760(99)00205-2","volume":"11","author":"S Nouet","year":"2000","unstructured":"Nouet S, Nahmias C. Signal transduction from the angiotensin II AT2 receptor. Trends Endocrinol Metab. 2000;11(1):1\u20136.","journal-title":"Trends Endocrinol Metab"},{"key":"4627_CR58","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k4209","volume":"363","author":"BM Hicks","year":"2018","unstructured":"Hicks BM, et al. Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study. BMJ. 2018;363: k4209.","journal-title":"BMJ"},{"issue":"3","key":"4627_CR59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers12030747","volume":"12","author":"SY Lin","year":"2020","unstructured":"Lin SY, et al. Association between angiotensin-converting enzyme inhibitors and lung cancer-a nationwide, population-based, propensity score-matched cohort study. Cancers (Basel). 2020;12(3):1.","journal-title":"Cancers (Basel)"},{"issue":"1","key":"4627_CR60","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1111\/j.1365-2125.2012.04170.x","volume":"74","author":"J Hallas","year":"2012","unstructured":"Hallas J, et al. Long term use of drugs affecting the renin-angiotensin system and the risk of cancer: a population-based case-control study. Br J Clin Pharmacol. 2012;74(1):180\u20138.","journal-title":"Br J Clin Pharmacol"},{"issue":"3","key":"4627_CR61","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s10238-020-00622-7","volume":"20","author":"L Smith","year":"2020","unstructured":"Smith L, et al. Cross-sectional associations between angiotensin-converting enzyme inhibitor use and cancer diagnosis in US adults. Clin Exp Med. 2020;20(3):409\u201316.","journal-title":"Clin Exp Med"},{"issue":"2","key":"4627_CR62","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.18632\/aging.102699","volume":"12","author":"Y Xie","year":"2020","unstructured":"Xie Y, et al. Antihypertensive medications are associated with the risk of kidney and bladder cancer: a systematic review and meta-analysis. Aging (Albany NY). 2020;12(2):1545\u201362.","journal-title":"Aging (Albany NY)"},{"issue":"4","key":"4627_CR63","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1093\/aje\/kww217","volume":"185","author":"MA Raebel","year":"2017","unstructured":"Raebel MA, et al. Risk of breast cancer with long-term use of calcium channel blockers or angiotensin-converting enzyme inhibitors among older women. Am J Epidemiol. 2017;185(4):264\u201373.","journal-title":"Am J Epidemiol"},{"issue":"3","key":"4627_CR64","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1161\/HYPERTENSIONAHA.120.15317","volume":"76","author":"KS Cheung","year":"2020","unstructured":"Cheung KS, et al. ACE (angiotensin-converting enzyme) inhibitors\/angiotensin receptor blockers are associated with lower colorectal cancer risk: a territory-wide study with propensity score analysis. Hypertension. 2020;76(3):968\u201375.","journal-title":"Hypertension"},{"issue":"1","key":"4627_CR65","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/jch.12228","volume":"16","author":"YY Chiang","year":"2014","unstructured":"Chiang YY, et al. Lowered cancer risk with ACE inhibitors\/ARBs: a population-based cohort study. J Clin Hypertens (Greenwich). 2014;16(1):27\u201333.","journal-title":"J Clin Hypertens (Greenwich)"},{"issue":"6","key":"4627_CR66","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1097\/EDE.0000000000001065","volume":"30","author":"PT Htoo","year":"2019","unstructured":"Htoo PT, et al. Renin-angiotensin-aldosterone system-based antihypertensive agents and the risk of colorectal cancer among medicare beneficiaries. Epidemiology. 2019;30(6):867\u201375.","journal-title":"Epidemiology"},{"key":"4627_CR67","first-page":"506","volume":"20","author":"M Hashemzehi","year":"2021","unstructured":"Hashemzehi M, et al. Angiotensin receptor blocker Losartan inhibits tumor growth of colorectal cancer. Excli J. 2021;20:506\u201321.","journal-title":"Excli J"},{"key":"4627_CR68","first-page":"927","volume":"19","author":"M Hashemzehi","year":"2020","unstructured":"Hashemzehi M, et al. The therapeutic potential of losartan in lung metastasis of colorectal cancer. Excli J. 2020;19:927\u201335.","journal-title":"Excli J"},{"issue":"12","key":"4627_CR69","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050893","volume":"7","author":"L Azoulay","year":"2012","unstructured":"Azoulay L, et al. Long-term use of angiotensin receptor blockers and the risk of cancer. PLoS ONE. 2012;7(12): e50893.","journal-title":"PLoS ONE"},{"issue":"4","key":"4627_CR70","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1158\/1078-0432.CCR-21-2105","volume":"28","author":"DP Regan","year":"2022","unstructured":"Regan DP, et al. Losartan blocks osteosarcoma-elicited monocyte recruitment, and combined with the kinase inhibitor toceranib, exerts significant clinical benefit in canine metastatic osteosarcoma. Clin Cancer Res. 2022;28(4):662\u201376.","journal-title":"Clin Cancer Res"},{"issue":"6","key":"4627_CR71","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1073\/pnas.1818357116","volume":"116","author":"Y Zhao","year":"2019","unstructured":"Zhao Y, et al. Losartan treatment enhances chemotherapy efficacy and reduces ascites in ovarian cancer models by normalizing the tumor stroma. Proc Natl Acad Sci USA. 2019;116(6):2210\u20139.","journal-title":"Proc Natl Acad Sci USA"},{"key":"4627_CR72","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.938439","volume":"13","author":"Q Zhao","year":"2022","unstructured":"Zhao Q, et al. Enhanced therapeutic efficacy of combining losartan and chemo-immunotherapy for triple negative breast cancer. Front Immunol. 2022;13: 938439.","journal-title":"Front Immunol"},{"issue":"14","key":"4627_CR73","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1096\/fj.03-0129com","volume":"17","author":"T Walther","year":"2003","unstructured":"Walther T, et al. Differential regulation of in vivo angiogenesis by angiotensin II receptors. Faseb J. 2003;17(14):2061\u20137.","journal-title":"Faseb J"},{"issue":"5","key":"4627_CR74","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1097\/MPA.0b013e3181c314cd","volume":"39","author":"Q Gong","year":"2010","unstructured":"Gong Q, et al. Blocking angiotensin II Type 1 receptor triggers apoptotic cell death in human pancreatic cancer cells. Pancreas. 2010;39(5):581\u201394.","journal-title":"Pancreas"},{"issue":"7","key":"4627_CR75","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1001\/jamaoncol.2019.0892","volume":"5","author":"JE Murphy","year":"2019","unstructured":"Murphy JE, et al. Total neoadjuvant therapy with FOLFIRINOX in combination with losartan followed by chemoradiotherapy for locally advanced pancreatic cancer: a phase 2 clinical trial. JAMA Oncol. 2019;5(7):1020\u20137.","journal-title":"JAMA Oncol"},{"issue":"1","key":"4627_CR76","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1186\/s12885-019-6242-8","volume":"19","author":"P Liu","year":"2019","unstructured":"Liu P, et al. Furosemide use and survival in patients with esophageal or gastric cancer: a population-based cohort study. BMC Cancer. 2019;19(1):1017.","journal-title":"BMC Cancer"},{"issue":"3","key":"4627_CR77","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/s41391-020-0220-8","volume":"23","author":"K Beckmann","year":"2020","unstructured":"Beckmann K, et al. Spironolactone use is associated with lower prostate cancer risk: a population-wide case-control study. Prostate Cancer Prostatic Dis. 2020;23(3):527\u201333.","journal-title":"Prostate Cancer Prostatic Dis"},{"issue":"6","key":"4627_CR78","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1002\/eji.201344265","volume":"44","author":"L Besedovsky","year":"2014","unstructured":"Besedovsky L, et al. Mineralocorticoid receptor signaling reduces numbers of circulating human na\u00efve T cells and increases their CD62L, CCR7, and CXCR4 expression. Eur J Immunol. 2014;44(6):1759\u201369.","journal-title":"Eur J Immunol"},{"issue":"4","key":"4627_CR79","doi-asserted-by":"publisher","first-page":"247","DOI":"10.14740\/jocmr3744","volume":"11","author":"D Shin","year":"2019","unstructured":"Shin D, et al. Association between the use of thiazide diuretics and the risk of skin cancers: a meta-analysis of observational studies. J Clin Med Res. 2019;11(4):247\u201355.","journal-title":"J Clin Med Res"},{"issue":"10","key":"4627_CR80","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1097\/HJH.0000000000002136","volume":"37","author":"R Kreutz","year":"2019","unstructured":"Kreutz R, Algharably EAH, Douros A. Reviewing the effects of thiazide and thiazide-like diuretics as photosensitizing drugs on the risk of skin cancer. J Hypertens. 2019;37(10):1950\u20138.","journal-title":"J Hypertens"},{"issue":"7","key":"4627_CR81","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1111\/bcp.14245","volume":"86","author":"DR Morales","year":"2020","unstructured":"Morales DR, et al. Association between hydrochlorothiazide exposure and different incident skin, lip and oral cavity cancers: a series of population-based nested case-control studies. Br J Clin Pharmacol. 2020;86(7):1336\u201345.","journal-title":"Br J Clin Pharmacol"},{"issue":"11","key":"4627_CR82","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1038\/s41416-019-0613-4","volume":"121","author":"A Potteg\u00e5rd","year":"2019","unstructured":"Potteg\u00e5rd A, et al. Use of hydrochlorothiazide and risk of skin cancer: a nationwide Taiwanese case-control study. Br J Cancer. 2019;121(11):973\u20138.","journal-title":"Br J Cancer"},{"issue":"4","key":"4627_CR83","doi-asserted-by":"publisher","first-page":"917","DOI":"10.3904\/kjim.2019.218","volume":"35","author":"E Park","year":"2020","unstructured":"Park E, Lee Y, Jue MS. Hydrochlorothiazide use and the risk of skin cancer in patients with hypertensive disorder: a nationwide retrospective cohort study from Korea. Korean J Intern Med. 2020;35(4):917\u201328.","journal-title":"Korean J Intern Med"},{"issue":"4","key":"4627_CR84","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1161\/CIRCRESAHA.114.302157","volume":"114","author":"J Wu","year":"2014","unstructured":"Wu J, et al. Inflammation and mechanical stretch promote aortic stiffening in hypertension through activation of p38 mitogen-activated protein kinase. Circ Res. 2014;114(4):616\u201325.","journal-title":"Circ Res"},{"issue":"1","key":"4627_CR85","doi-asserted-by":"publisher","first-page":"4271","DOI":"10.1038\/s41598-020-61162-4","volume":"10","author":"H Cui","year":"2020","unstructured":"Cui H, et al. Identification of the key genes and pathways involved in the tumorigenesis and prognosis of kidney renal clear cell carcinoma. Sci Rep. 2020;10(1):4271.","journal-title":"Sci Rep"},{"issue":"12","key":"4627_CR86","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1007\/s00432-011-1050-9","volume":"137","author":"L Xie","year":"2011","unstructured":"Xie L, et al. Solute carrier protein family may involve in radiation-induced radioresistance of non-small cell lung cancer. J Cancer Res Clin Oncol. 2011;137(12):1739\u201347.","journal-title":"J Cancer Res Clin Oncol"}],"container-title":["Journal of Orthopaedic Surgery and Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13018-024-04627-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13018-024-04627-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13018-024-04627-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T10:15:51Z","timestamp":1708337751000},"score":1,"resource":{"primary":{"URL":"https:\/\/josr-online.biomedcentral.com\/articles\/10.1186\/s13018-024-04627-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,19]]},"references-count":86,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["4627"],"URL":"https:\/\/doi.org\/10.1186\/s13018-024-04627-w","relation":{},"ISSN":["1749-799X"],"issn-type":[{"value":"1749-799X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,19]]},"assertion":[{"value":"10 November 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"147"}}