{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T03:06:23Z","timestamp":1775099183030,"version":"3.50.1"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology and Applied Pharmacology"],"published-print":{"date-parts":[[2021,5]]},"DOI":"10.1016\/j.taap.2021.115491","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T01:03:46Z","timestamp":1616029426000},"page":"115491","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["Pyrazole (1, 2-diazole) induce apoptosis in lymphoma cells by targeting BCL-2 and BCL-XL genes and mitigate murine solid tumour development by regulating cyclin-D1 and Ki-67 expression"],"prefix":"10.1016","volume":"418","author":[{"given":"Walsan Kalarikkal","family":"Vishnu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prathapan","family":"Abeesh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandrasekharan","family":"Guruvayoorappan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.taap.2021.115491_bb0005","article-title":"Phase I and clinical pharmacological evaluation of pirozantrone hydrochloride (oxantrazole)","volume":"50","author":"Ames","year":"1990","journal-title":"Cancer Res."},{"key":"10.1016\/j.taap.2021.115491_bb0010","doi-asserted-by":"crossref","first-page":"103470","DOI":"10.1016\/j.bioorg.2019.103470","article-title":"Overview of recent developments of pyrazole derivatives as an anticancer agent in different cell line","volume":"97","author":"Bennani","year":"2020","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.taap.2021.115491_bb0015","doi-asserted-by":"crossref","first-page":"8519","DOI":"10.1200\/JCO.2018.36.15_suppl.8519","article-title":"Efficacy of milciclib (PHA-848125AC), a pan-cyclin d-dependent kinase inhibitor, in two phase II studies with thymic carcinoma (TC) and B3 thymoma (B3T) patients","volume":"36","author":"Besse","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.taap.2021.115491_bb0020","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.3892\/ol.2014.2345","article-title":"Mechanisms of coagulative necrosis in malignant epithelial tumors (review)","volume":"8","author":"Caruso","year":"2014","journal-title":"Oncol. Lett."},{"key":"10.1016\/j.taap.2021.115491_bb0025","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1038\/bjc.2014.565","article-title":"A phase i study of cyclin-dependent kinase inhibitor, AT7519, in patients with advanced cancer: NCIC Clinical Trials Group IND 177","volume":"111","author":"Chen","year":"2014","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.taap.2021.115491_bb0030","doi-asserted-by":"crossref","DOI":"10.21769\/BioProtoc.3465","article-title":"Semi-quantitative determination of protein expression using immunohistochemistry staining and analysis: an integrated protocol","volume":"9","author":"Crowe","year":"2019","journal-title":"Bio-Protocol."},{"key":"10.1016\/j.taap.2021.115491_bb0035","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.etp.2011.08.009","article-title":"Preliminary evaluation of in vitro cytotoxicity and in vivo antitumor activity of Premna herbacea Roxb. in Ehrlich ascites carcinoma model and Dalton\u2019s lymphoma ascites model","volume":"65","author":"Dhamija","year":"2013","journal-title":"Exp. Toxicol. Pathol."},{"key":"10.1016\/j.taap.2021.115491_bb0040","doi-asserted-by":"crossref","first-page":"226","DOI":"10.4161\/cbt.72","article-title":"Cycling to cancer with cyclin D1","volume":"1","author":"Diehl","year":"2002","journal-title":"Cancer Biol. Ther."},{"key":"10.1016\/j.taap.2021.115491_bb0045","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: a review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"10.1016\/j.taap.2021.115491_bb0050","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1038\/nrc1736","article-title":"Promoting apoptosis as a strategy for cancer drug discovery","volume":"5","author":"Fesik","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.taap.2021.115491_bb0055","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1051\/mmnp\/20127102","article-title":"Cancer as multifaceted disease","volume":"7","author":"Friedman","year":"2012","journal-title":"Math. Model. Nat. Phenom."},{"key":"10.1016\/j.taap.2021.115491_bb0060","doi-asserted-by":"crossref","DOI":"10.1155\/2013\/486419","article-title":"Antigenotoxic and apoptotic activity of green tea polyphenol extracts on hexavalent chromium-induced DNA damage in peripheral blood of CD-1 mice: analysis with differential acridine orange\/ethidium bromide staining","author":"Garc\u00eda-Rodr\u00edguez","year":"2013","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.taap.2021.115491_bb0065","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/nrc.2017.92","article-title":"Preclinical mouse solid tumour models: status quo, challenges and perspectives","volume":"17","author":"Gengenbacher","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.taap.2021.115491_bb0070","first-page":"17","article-title":"A review on laboratory liver function tests","volume":"3","author":"Gowda","year":"2009","journal-title":"Pan Afr. Med. J."},{"key":"10.1016\/j.taap.2021.115491_bb0075","first-page":"27","article-title":"Immunomodulatory and antitumor activity of Biophytum sensitivum extract","volume":"8","author":"Guruvayoorappan","year":"2007","journal-title":"Asian Pacific J. Cancer Prev."},{"key":"10.1016\/j.taap.2021.115491_bb0080","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"10.1016\/j.taap.2021.115491_bb0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.immuni.2021.01.017","article-title":"Leveraging the antiviral type I interferon system as a first line of defense against SARS-CoV-2 pathogenicity","author":"Hoagland","year":"2021","journal-title":"Immunity"},{"key":"10.1016\/j.taap.2021.115491_bb0090","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nrc776","article-title":"Death and anti-death: tumour resistance to apoptosis","volume":"2","author":"Igney","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.taap.2021.115491_bb0095","article-title":"Aberrant expression of cyclin D1 in cancer","volume":"4","author":"Inoue","year":"2015","journal-title":"Sign. Transduct. Insights"},{"key":"10.1016\/j.taap.2021.115491_bb0100","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.tranon.2014.07.003","article-title":"Co-encapsulation of doxorubicin with galactoxyloglucan nanoparticles for intracellular tumor-targeted delivery in murine ascites and solid tumors","volume":"7","author":"Joseph","year":"2014","journal-title":"Transl. Oncol."},{"key":"10.1016\/j.taap.2021.115491_bb0105","first-page":"1073","article-title":"Anemia in metastatic solid tumors : a frequent and serious finding. Small review of the literature","volume":"5","author":"Jounblat","year":"2017","journal-title":"J. Hematol. Transfus."},{"key":"10.1016\/j.taap.2021.115491_bb0110","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/cdd.2017.186","article-title":"BCL-2 family proteins: changing partners in the dance towards death","volume":"25","author":"Kale","year":"2018","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.taap.2021.115491_bb0115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/molecules23010134","article-title":"Synthesis and pharmacological activities of Pyrazole derivatives: a review","volume":"23","author":"Karrouchi","year":"2018","journal-title":"Molecules"},{"key":"10.1016\/j.taap.2021.115491_bb0120","doi-asserted-by":"crossref","first-page":"6194","DOI":"10.1038\/onc.2008.297","article-title":"Caspases in apoptosis and beyond","volume":"27","author":"Li","year":"2008","journal-title":"Oncogene"},{"key":"10.1016\/j.taap.2021.115491_bb0125","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1136\/pmj.79.932.307","article-title":"Evaluation of abnormal liver function tests","volume":"79","author":"Limdi","year":"2003","journal-title":"Postgrad. Med. J."},{"key":"10.1016\/j.taap.2021.115491_bb0130","series-title":"Cancer Statistics, 2020: Report from National Cancer Registry Programme","author":"Mathur","year":"2020"},{"key":"10.1016\/j.taap.2021.115491_bb0135","doi-asserted-by":"crossref","first-page":"448","DOI":"10.3390\/ijms19020448","article-title":"Apoptosis: a target for anticancer therapy","volume":"19","author":"Pfeffer","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.taap.2021.115491_bb0140","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1007\/s00109-016-1475-3","article-title":"Cyclin D1, cancer progression, and opportunities in cancer treatment","volume":"94","author":"Qie","year":"2016","journal-title":"J. Mol. Med."},{"key":"10.1016\/j.taap.2021.115491_bb0145","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1023\/A:1007429904664","article-title":"Apoptosis: identification of dying cells","volume":"14","author":"Renvoiz\u00e9","year":"1998","journal-title":"Cell Biol. Toxicol."},{"key":"10.1016\/j.taap.2021.115491_bb0150","first-page":"3989","article-title":"Anticancer activity of Acacia nilotica (L.) Wild. Ex. Delile subsp. INDICA against dalton\u2019s ascitic lymphoma induced solid and ascitic tumor model, Asian Pacific","volume":"13","author":"Sakthivel","year":"2012","journal-title":"J. Cancer Prev."},{"key":"10.1016\/j.taap.2021.115491_bb0155","doi-asserted-by":"crossref","first-page":"917","DOI":"10.3389\/fchem.2019.00917","article-title":"Novel anticancer fused Pyrazole derivatives as EGFR and VEGFR-2 dual TK inhibitors","volume":"7","author":"Saleh","year":"2020","journal-title":"Front. Chem."},{"key":"10.1016\/j.taap.2021.115491_bb0160","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/S0008-6363(99)00384-3","article-title":"Morphologic and biochemical hallmarks of apoptosis","volume":"45","author":"Saraste","year":"2000","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.taap.2021.115491_bb0165","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"10.1016\/j.taap.2021.115491_bb0170","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9","article-title":"The Ki-67 protein: from the known and the unknown","volume":"182","author":"Scholzen","year":"2000","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.taap.2021.115491_bb0175","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3109\/1547691X.2012.660997","article-title":"Anti-inflammatory and anti-tumor activity of the marine mangrove Rhizophora apiculata","volume":"9","author":"Vinod Prabhu","year":"2012","journal-title":"J. Immunotoxicol."},{"key":"10.1016\/j.taap.2021.115491_bb0180","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.7314\/APJCP.2013.14.3.1833","article-title":"Inhibition of metastatic lung cancer in C57BL\/6 mice by marine mangrove Rhizophora apiculata","volume":"14","author":"Vinod Prabhu","year":"2013","journal-title":"Asian Pacific J. Cancer Prev."},{"key":"10.1016\/j.taap.2021.115491_bb0185","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.gene.2018.09.014","article-title":"Targeting apoptosis by 1,2-diazole through regulation of EGFR, Bcl-2 and CDK-2 mediated signaling pathway in human non-small cell lung carcinoma A549 cells","volume":"679","author":"Vinod Prabhu","year":"2018","journal-title":"Gene"},{"key":"10.1016\/j.taap.2021.115491_bb0190","article-title":"Targeting NF-\u03baB mediated cell signaling pathway and inflammatory mediators by 1,2-diazole in A549 cells in vitro","volume":"29","author":"Vinod Prabhu","year":"2021","journal-title":"Biotechnol. Rep."},{"key":"10.1016\/j.taap.2021.115491_bb0195","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/1756-9966-30-87","article-title":"Apoptosis in cancer: from pathogenesis to treatment","volume":"30","author":"Wong","year":"2011","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"10.1016\/j.taap.2021.115491_bb0200","series-title":"World Health Statistics 2020: Monitoring Health for the SDGs, Sustainable Development Goals","author":"World Health Organization (WHO)","year":"2020"},{"key":"10.1016\/j.taap.2021.115491_bb0205","first-page":"1849","article-title":"Phase I clinical evaluation of 2,3-dihydro-1H-imidazo[1,2-b]pyrazole","volume":"63","author":"Yap","year":"1979","journal-title":"Cancer Treat. Rep."},{"key":"10.1016\/j.taap.2021.115491_bb0210","doi-asserted-by":"crossref","DOI":"10.4137\/CGM.S37907","article-title":"Animal models of cancer biology","volume":"8s1","author":"Yee","year":"2015","journal-title":"Cancer Growth Metastasis"},{"key":"10.1016\/j.taap.2021.115491_bb0215","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrm2308","article-title":"The BCL-2 protein family: opposing activities that mediate cell death","volume":"9","author":"Youle","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.taap.2021.115491_bb0220","first-page":"1","article-title":"Overcoming cancer therapeutic bottleneck by drug repurposing","volume":"5","author":"Zhang","year":"2020","journal-title":"Signal Transduct. Target. Ther."}],"container-title":["Toxicology and Applied Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X21000983?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X21000983?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T20:53:50Z","timestamp":1758574430000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041008X21000983"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5]]},"references-count":44,"alternative-id":["S0041008X21000983"],"URL":"https:\/\/doi.org\/10.1016\/j.taap.2021.115491","relation":{},"ISSN":["0041-008X"],"issn-type":[{"value":"0041-008X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pyrazole (1, 2-diazole) induce apoptosis in lymphoma cells by targeting BCL-2 and BCL-XL genes and mitigate murine solid tumour development by regulating cyclin-D1 and Ki-67 expression","name":"articletitle","label":"Article Title"},{"value":"Toxicology and Applied Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.taap.2021.115491","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"115491"}}