The DOI matches its Crossref record; 31 of the 35 references it cites were found in a registry or an index.
Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis.
Abstract
Objectives Elevated circulating levels of interleukin 6 (IL-6) have been associated with cancer metastasis. IL-6 binds either to membrane or to soluble IL-6 receptor (IL-6sR), which then induces homodimerization of gp130 that activates downstream signaling. We tested the hypothesis that preoperative plasma IL-6 and IL-6sR levels are associated with prostate cancer stage, progression, and metastasis after radical prostatectomy.Methods Plasma levels of IL-6 and IL-6sR were measured in 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer, 44 healthy men without any cancer, 19 men with prostate cancer metastatic to the regional lymph nodes, and 10 men with prostate cancer metastatic to bone.Results Plasma IL-6 and IL-6sR levels were highest in patients with bone metastases (P <0.001). The preoperative IL-6 and IL-6sR levels were associated with the preoperative prostate-specific antigen (PSA) level (P </=0.041), prostatectomy tumor volume (P </=0.048), and final Gleason sum (P </=0.042). The preoperative IL-6 and IL-6sR levels and biopsy Gleason sum were independent predictors of PSA progression (P </=0.029). However, in a model that included both IL-6 and IL-6sR, only IL-6sR and the biopsy Gleason sum predicted progression (P </=0.040). In patients whose disease progressed, the preoperative IL-6 and IL-6sR levels were highest in those with presumed aggressive failure (P </=0.042).Conclusions Plasma IL-6 and IL-6sR levels were dramatically elevated in the men with prostate cancer metastatic to bone. In patients with clinically localized prostate cancer, the preoperative plasma IL-6 and IL-6sR levels independently predicted biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“The levels of IL-6 and its soluble receptor, IL-6sR, in circulating plasma is increased in patients with aggressive metastatic disease and can be predictive of recurrence after treatment of localized cancer (17).”
From Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer (2011) · cites this paper as [17]
Citations
Cites
Natural History of Progression After PSA Elevation Following Radical Prostatectomy
Pound, C. R. (1999) · JAMA · doi:10.1001/jama.281.17.1591 · Cited by 3,077
A Preoperative Nomogram for Disease Recurrence Following Radical Prostatectomy for Prostate Cancer
Kattan, M. W., Eastham, J. A., Stapleton, A. M. F., Wheeler, T. M., & Scardino, P. T. (1998) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/90.10.766 · Cited by 1,243
IL-6 is produced by osteoblasts and induces bone resorption.
Ishimi, Y., Miyaura, C., Jin, C., Akatsu, T., Abe, E., Nakamura, Y. K., Yamaguchi, A., Yoshiki, S., Matsuda, T., Hirano, T., et al. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.145.10.3297 · Cited by 1,128
Soluble receptors for cytokines and growth factors: generation and biological function
Rose‐John, S., & Heinrich, P. C. (1994) · Biochemical Journal · doi:10.1042/bj3000281 · Cited by 777
Evidence for the involvement of interleukin 6 in experimental cancer cachexia.
Strassmann, G., Fong, M., Kenney, J. S., & Jacob, C. O. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115767 · Cited by 660
Prediction of Progression Following Radical Prostatectomy
Epstein, J. I., Partin, A. W., Sauvageot, J., & Walsh, P. C. (1996) · The American Journal of Surgical Pathology · doi:10.1097/00000478-199603000-00004 · Cited by 560
Hobisch, A., Eder, I. E., Putz, T., Horninger, W., Bartsch, G. C., Klocker, H., & Čulig, Z. (1998) · PubMed · Cited by 437
Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma.
Blay, J., Négrier, S., Combaret, V., Attali, S., Goillot, E., Merrouche, Y., Mercatello, A., Ravault, A., Tourani, J. M., & Jf, M. (1992) · PubMed · Cited by 420
Adler, H. L., McCURDY, M. A., Kattan, M. W., Timme, T. L., Scardino, P. T., & Thompson, T. C. (1999) · The Journal of Urology · doi:10.1016/s0022-5347(01)62092-5 · Cited by 387
Serum interleukin 6 as a prognostic factor in patients with prostate cancer.
Nakashima, J., Tachibana, M., Horiguchi, Y., Oya, M., Ohigashi, T., Asakura, H., & Murai, M. (2000) · PubMed · Cited by 351
Cited by
Sorted by citations
Interleukin-6 in Aging and Chronic Disease: A Magnificent Pathway
Maggio, M. G., Guralnik, J. M., Longo, D. L., & Ferrucci, L. (2006) · The Journals of Gerontology Series A · doi:10.1093/gerona/61.6.575 · Cited by 696
Human prostate cancer risk factors
Bostwick, D. G., BURKE, H. B., Djakiew, D., Euling, S. Y., Ho, S., Landolph, J. R., MORRISON, H. I., Sonawane, B. R., Shifflett, T., Waters, D. J., et al. (2004) · Cancer · doi:10.1002/cncr.20408 · Cited by 675
Obesity and Prostate Cancer: Weighing the Evidence
Allott, E. H., Masko, E. M., & Freedland, S. J. (2012) · European Urology · doi:10.1016/j.eururo.2012.11.013 · Cited by 623
“Circulating IL-6 levels are elevated in PCa patients with metastatic relative to organ-confined disease [73,74], and they are associated with time to progression to metastatic disease [75].”
BackgroundLahn, M. M. F., Herbertz, S., Sawyer, J. S., Stauber, A. J., Gueorguieva, I., Driscoll, K. E., Estrem, S. T., Cleverly, A., Desaiah, D., Guba, S. C., et al. (2015) · Drug Design Development and Therapy · doi:10.2147/dddt.s86621 · Cited by 571
Androgen receptor signaling in prostate cancer development and progression
Tindall, D. J., & Lonergan, P. E. (2011) · Journal of Carcinogenesis · doi:10.4103/1477-3163.83937 · Cited by 544
Michalaki, V., Syrigos, K., Charles, P., & Waxman, J. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6601814 · Cited by 406
“IL-6 and TNF-a, two cytokines with multiple and overlapping biological properties, are involved in prostate cancer development (Shariat et al, 2001; Smith et al, 2001).”
Androgen receptor: A key molecule in the progression of prostate cancer to hormone independence
Taplin, M., & Balk, S. P. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10653 · Cited by 392
Inflammation and prostate cancer: the role of interleukin 6 ( IL ‐6)
Nguyen, D. P., Li, J., & Tewari, A. K. (2013) · British Journal of Urology · doi:10.1111/bju.12452 · Cited by 357
Bone Loss following Hypogonadism in Men with Prostate Cancer Treated with GnRH Analogs
Mittan, D., Lee, S., Miller, E. P., Perez, R., Basler, J. W., & Bruder, J. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.8.8782 · Cited by 278
E., O. I., McGaw, L. J., Naidoo, V., & Eloff, J. N. (2007) · AFRICAN JOURNAL OF BIOTECHNOLOGY · doi:10.5897/ajb2007.000-2457 · Cited by 250
“Cancer Increases IL-6 and IL-6sR are associated with progression and metastasis of prostate cancer (Shariat et al., 2001).”
BackgroundEpidemiology of Inflammation and Prostate Cancer
Platz, E. A., & Marzo, A. M. D. (2004) · The Journal of Urology · doi:10.1097/01.ju.0000108131.43160.77 · Cited by 246
Yuan, T., Veeramani, S., & Lin, M. (2007) · Endocrine Related Cancer · doi:10.1677/erc-07-0061 · Cited by 232
“Results of clinical studies reveal that the serum level of interleukin-6 (IL-6) is elevated in patients with PCa, especially hormonerefractory and metastatic PCa (Adler et al. 1999, Drachenberg et al. 1999, Shariat et al. 2001).”
BackgroundKattan, M. W., Shariat, S. F., Andrews, B., Zhu, K., Canto, E. A., Matsumoto, K., Muramoto, M., Scardino, P. T., Ohori, M., Wheeler, T. M., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.12.037 · Cited by 208
The role of transsignalling via the agonistic soluble IL-6 receptor in human diseases
Kallen, K. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(02)00325-7 · Cited by 205
Fizazi, K. S., Bono, J. S. D., Fléchon, A., Heidenreich, A., Voog, É., Davis, N. B., Qi, M., Bandekar, R. R., VERMEULEN, J. T., Cornfeld, M. J., et al. (2011) · European Journal of Cancer · doi:10.1016/j.ejca.2011.10.014 · Cited by 198
Systematic review of the association between circulating interleukin-6 (IL-6) and cancer
Heikkilä, K., Ebrahim, S., & Lawlor, D. A. (2008) · European Journal of Cancer · doi:10.1016/j.ejca.2008.02.047 · Cited by 232
Tumor markers in prostate cancer I: Blood-based markers
Shariat, S. F., Semjonow, A., Lilja, H. G., Savage, C. J., Vickers, A. J., & Bjartell, A. S. (2011) · Acta Oncologica · doi:10.3109/0284186x.2010.542174 · Cited by 174
McCarty, M. F. (2004) · Integrative Cancer Therapies · doi:10.1177/1534735404270757 · Cited by 170
“Serum levels of IL-6 and of IL-6 receptors are typically elevated in patients with advanced prostate cancer, particularly bone metastases, and correlate with poor prognosis.(347,361,362) In the PC-3 and DU145 cell lines, increased activity”
BackgroundElevation of cytokine levels in cachectic patients with prostate carcinoma
Pfitzenmaier, J., Vessella, R. L., Higano, C. S., Noteboom, J. L., Wallace, D., & Corey, E. (2003) · Cancer · doi:10.1002/cncr.11178 · Cited by 167
“Shariat et al.(24) reported increased levels of IL-6 in patients with CaP who had bone metastases, and Wise et al.”
BackgroundShariat, S. F., Kattan, M. W., Traxel, E. J., Andrews, B., Zhu, K., Wheeler, T. M., & Slawin, K. M. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-0768-03 · Cited by 166
“Remarkably, we recently demonstrated that in patients undergoing radical prostatectomy for clinically localized disease, preoperative plasma TGF- 1, IL-6, and IL-6sR were associated with eventual prostate cancer progression, when adjusted for the effects of clinical stage, biopsy Gleason sum and preoperative PSA (16,…”
BackgroundMethodResultInfluentialCytokines and Chemokines as Mediators of Prostate Cancer Metastasis
Adekoya, T. O., & Richardson, R. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124449 · Cited by 160
“In bone metastatic patients for example, levels of both IL-6 and soluble IL-6 receptor (IL-6-SR) has been found to be increased [188].”
BackgroundEmerging Biomarkers for the Diagnosis and Prognosis of Prostate Cancer
Sardana, G., Dowell, B. L., & Diamandis, E. P. (2008) · Clinical Chemistry · doi:10.1373/clinchem.2008.110668 · Cited by 156
“Increased concentrations of IL-6 and its receptor have been demonstrated in metastatic and androgen-independent CaP ( 66 ) and have been suggested as candidate markers of CaP progression (67).”
BackgroundMinireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer
Lamont, K. R., & Tindall, D. J. (2011) · Molecular Endocrinology · doi:10.1210/me.2010-0469 · Cited by 150
“The levels of IL-6 and its soluble receptor, IL-6sR, in circulating plasma is increased in patients with aggressive metastatic disease and can be predictive of recurrence after treatment of localized cancer (17).”
BackgroundCancer-associated bone disease
Rizzoli, R., Body, J. J., Brandi, M. L., Cannata-Andía, J. B., Chappard, D., Maghraoui, A. E., Glüer, C.-C., Kendler, D., Napoli, N., Παπαϊωάννου, Α., et al. (2013) · Osteoporosis International · doi:10.1007/s00198-013-2530-3 · Cited by 155
“In turn, activated osteoblasts can release large amounts of IL-6, TGF-β, PDGF-BB which are potent growth factors for the tumour cells [32-34].”
BackgroundPeriprostatic Adipose Tissue as a Modulator of Prostate Cancer Aggressiveness
Finley, D. S., Calvert, V. S., Inokuchi, J., Lau, A., Narula, N., Petricoin, E. F., Zaldivar, F. P., Santos, R. T., Tyson, D. R., & Ornstein, D. K. (2009) · The Journal of Urology · doi:10.1016/j.juro.2009.06.015 · Cited by 152
Jorcyk, C. L., Tawara, K., & Jorcyk, C. L. (2011) · Cancer Management and Research · doi:10.2147/cmr.s18101 · Cited by 153
Visceral Fat Accumulation as a Risk Factor for Prostate Cancer
HAFE, P. V., Pina, F., Pérez, A., Tavares, M., & Barros, H. (2004) · Obesity Research · doi:10.1038/oby.2004.242 · Cited by 144
Prostate tumor-stroma interaction: molecular mechanisms and opportunities for therapeutic targeting
Sung, S., & Chung, L. W. K. (2002) · Differentiation · doi:10.1046/j.1432-0436.2002.700905.x · Cited by 137
Wu, B. J., Yin, L., Shi, C., Li, Q., Duan, P., Huang, J.-M., Liu, C., Wang, F., Lewis, M. S., Wang, Y., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.02.003 · Cited by 135
“IL6 has been implicated in bone metastasis (Shariat et al., 2001) and has been associated with poor clinical outcomes (Nakashima et al., 2000).”
BackgroundYoon, Y., Liang, Z., Zhang, X., Choe, M., Zhu, A., Cho, H. T., Shin, D. M., Goodman, M. M., Chen, Z., & Shim, H. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2263 · Cited by 134
Obesity, Adipokines, and Prostate Cancer in a Prospective Population-Based Study
Baillargeon, J., Platz, E. A., Rose, D. P., Pollock, B. H., Ankerst, D. P., Haffner, S. M., Higgins, B., Lokshin, A. E., Troyer, D. A., Hernández, J., et al. (2006) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-06-0082 · Cited by 134
“In prostate cancer patients, elevated circulating IL-6 levels have been associated with advanced disease stage, distant metastasis, metastasis-related morbidity, and decreased overall survival (29, 33-35).”
BackgroundMcKenzie, S. P., & Kyprianou, N. (2005) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20634 · Cited by 130
“Furthermore, preoperative serum IL-6 measurements appear to be an effective screening tool for occult metastatic disease at the time of resection [Shariat et al., 2001] and may prove valuable in the development of adjuvant therapy protocols.”
BackgroundExercise-induced myokines and their effect on prostate cancer
Kim, J., Galvao, D. A., Newton, R. U., Gray, E. S., & Taaffe, D. R. (2021) · Nature Reviews Urology · doi:10.1038/s41585-021-00476-y · Cited by 131
IL-6/IL-6R as a potential key signaling pathway in prostate cancer development
Azevedo, A. S. (2011) · World Journal of Clinical Oncology · doi:10.5306/wjco.v2.i12.384 · Cited by 122
Santer, F. R., Malinowska, K., Čulig, Z., & Cavarretta, I. T. R. (2009) · Endocrine Related Cancer · doi:10.1677/erc-09-0200 · Cited by 119
“Collectively, these data suggest that selective targeting of IL-6TS might allow to refine the currently available experimental anti-IL-6 therapies against PC. Endocrine-Related Cancer (2010) 17 241–253”
BackgroundResultMean platelet volume could be possible biomarker in early diagnosis and monitoring of gastric cancer
Kılınçalp, S., Ekız, F., Başar, Ö., Mehmet Raşit, A. Y. T. E., Çoban, Ş., Yılmaz, B., Altınbaş, A., Başar, N., Aktaş, B., Tuna, Y., et al. (2013) · Platelets · doi:10.3109/09537104.2013.783689 · Cited by 114
“Elevated serum concentrations of pro-inflammatory cytokines such as IL-6 were found significantly higher in individuals with gastric cancer, as well as in patients with other inflammation related cancers, such as colon and prostate cancers [28, 29].”
BackgroundExpression of STAT3 in Prostate Cancer Metastases
Don‐Doncow, N., Marginean, F. E., Coleman, I. M., Nelson, P. S., Ehrnström, R. A., Krzyzanowska, A., Morrissey, C. M., Hellsten, R., & Bjartell, A. S. (2016) · European Urology · doi:10.1016/j.eururo.2016.06.018 · Cited by 112
“Published by Elsevier shown that IL6 is a main driving force in pSTAT3 activation, and is highly expressed in PCa patients with poor prognostic outcome [5].”
BackgroundIL6 Receptor Blockade Enhances Chemotherapy Efficacy in Pancreatic Ductal Adenocarcinoma
Long, K. B., Tooker, G. M., Tooker, E., Luque, S. L., Lee, J. W., Pan, X., & Beatty, G. L. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0899 · Cited by 112
“sIL6R levels are naturally detected in the circulation (38), but are increased in patients with cancer that could lead to the formation of IL6/sIL6R complexes and subsequent IL6 trans-signaling (39, 40).”
BackgroundRoyuela, M., Ricote, M., Parsons, M. S., García‐Tuñón, I., Paniagua, R., & Miguel, M. P. D. (2003) · The Journal of Pathology · doi:10.1002/path.1476 · Cited by 110
Inder, K. L., Ruelcke, J. E., Petelin, L., Moon, H., Choi, E. A., Rae, J., Blumenthal, A., Hutmacher, D. W., Saunders, N. A., Stow, J. L., et al. (2014) · Journal of Extracellular Vesicles · doi:10.3402/jev.v3.23784 · Cited by 101
Wang, Y., Li, L., Guo, X., Jin, X., Sun, W., Zhang, X., & Xu, R. C. (2012) · Cytokine · doi:10.1016/j.cyto.2012.04.020 · Cited by 102
Liu, C., Zhu, Y., Lou, W., Cui, Y., Evans, C. P., & Gao, A. C. (2013) · The Prostate · doi:10.1002/pros.22741 · Cited by 101
Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone
Lü, Y., Chen, Q., Corey, E., Xie, W., Fan, J., Mizokami, A., & Zhang, J. (2008) · Clinical & Experimental Metastasis · doi:10.1007/s10585-008-9226-7 · Cited by 102
SRC-3/AIB1: transcriptional coactivator in oncogenesis1
Yan, J., Tsai, S. Y., & Tsai, M. (2006) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2006.00315.x · Cited by 99
Virk, M. S., & Lieberman, J. R. (2007) · Arthritis Research & Therapy · doi:10.1186/ar2169 · Cited by 101
“IL-6 Regulates osteoblast function [88]”
Inflammation and Cancer: When NF-κB Amalgamates the Perilous Partnership
Dobrovolskaia, M. A., & Kozlov, S. (2005) · Current Cancer Drug Targets · doi:10.2174/1568009054629645 · Cited by 96
Endothelial Cells Enhance Prostate Cancer Metastasis via IL-6→Androgen Receptor→TGF-β→MMP-9 Signals
Wang, X., Lee, S. O., Xia, S., Jiang, Q., Luo, J., Li, L., Yeh, S., & Chang, C. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-0895 · Cited by 95
“IL-6 has been considered as an important growth-regulatory factor in human prostate cancer (21, 24) and has roles in metastases and morbidity (25).”
BackgroundRicote, M., García‐Tuñón, I., de Bethencourt, F. R., Fraile, B., Paniagua, R., & Royuela, M. (2004) · Cancer · doi:10.1002/cncr.20142 · Cited by 94
Oncogenic Ras-Induced Expression of Cytokines: A New Target of Anti-Cancer Therapeutics
Ancrile, B. B., O’Hayer, K., & Counter, C. M. (2008) · Molecular Interventions · doi:10.1124/mi.8.1.6 · Cited by 91
Belluco, C., Olivieri, F., Bonafè, M., Giovagnetti, S., Mammano, E., Scalerta, R., Ambrosi, A., Franceschi, C., Nitti, D., & Lise, M. (2003) · PubMed · Cited by 90
Immunotherapy for Prostate Cancer: Lessons from Responses to Tumor-Associated Antigens
Westdorp, H., Sköld, A. E., Snijer, B. A., Franik, S., Mulder, S. F., Major, P. P., Foley, R., Gerritsen, W. R., & de Vries, I. J. M. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00191 · Cited by 92
“IL-6 have been associated with more aggressive cancer progression and decreased survival in PCa (142).”
BackgroundSnoussi, K., Strosberg, A. D., Bouaouina, N., Ahmed, S. B., & Chouchane, L. (2005) · PubMed · Cited by 85
gp130: a promising drug target for cancer therapy
Xu, S., & Neamati, N. (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.830105 · Cited by 83
“Clinically, plasma IL-6 and sIL-6R levels were significantly elevated in association with prostate cancer progression and metastasis [89].”
BackgroundAre inflammatory cytokines the common link between cancer-associated cachexia and depression?
Illman, J., Corringham, R. E., Robinson, D., Davis, H. M., Rossi, J., Cella, D. F., & Trikha, M. (2005) · PubMed · Cited by 85
Osteomimicry how tumor cells try to deceive the bone
Teti, A. M. (2010) · Frontiers in Bioscience-Scholar · doi:10.2741/s110 · Cited by 80
Xiao, W., Hodge, D. R., Wang, L., Yang, X., Zhang, X., & Farrar, W. L. (2004) · The Prostate · doi:10.1002/pros.20113 · Cited by 83
“Increased IL-6 has been found in both serum [6,7] and prostate cancer tissues [5,8] in patients with metastatic prostate cancer, and can accelerate the growth of the human prostate carcinoma cancer cell line LNCaP in serum free medium [9].”
BackgroundShariat, S. F., Karam, J. A., Walz, J. C., Roehrborn, C. G., Montorsi, F., Margulis, V., Fred Saad, C., Slawin, K. M., & Karakiewicz, P. I. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4969 · Cited by 80
Chen, J., Zhang, D., Yan, W., Yang, D., & Shen, B. (2013) · BioMed Research International · doi:10.1155/2013/901578 · Cited by 86
“Increased serum levels of IL-6 and its receptor (IL-6R) are associated with metastatic and hormone refractory disease [19].”
BackgroundMonocyte Chemotactic Protein 1 Promotes Lung Cancer–Induced Bone Resorptive Lesions In Vivo
Cai, Z. Y., Chen, Q., Chen, J., Lü, Y., Xiao, G., Wu, Z., Zhou, Q., & Zhang, J. (2009) · Neoplasia · doi:10.1593/neo.81282 · Cited by 78
“These cancers include various types of cancer, such as prostate and breast cancers, which are the tumors that preferentiallymetastasize to bone [15,30,34,35,37,38].”
BackgroundShenderov, E., Boudadi, K., Fu, W., Wang, H., Sullivan, R., Jordan, A., Dowling, D., Harb, R., Schonhoft, J. D., Jendrisak, A., et al. (2021) · The Prostate · doi:10.1002/pros.24110 · Cited by 75
The potential role of vitamin C in empowering cancer immunotherapy
Bedhiafi, T., Inchakalody, V. P., Fernandes, Q., Mestiri, S., Billa, N., Shahab Uddin, M. S., Merhi, M., & Dermime, S. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112553 · Cited by 77
Flanagan, J., Gray, P. K., Hahn, N. M., Hayes, J., Myers, L. J., Carney, C. P., & Sweeney, C. J. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq443 · Cited by 75
Paule, B., Terry, S., Kheuang, L., Soyeux, P., Vacherot, F., & TAILLE, A. D. L. (2007) · World Journal of Urology · doi:10.1007/s00345-007-0175-6 · Cited by 79
“an increased production of IL-6 are associated in the advance of bone metastases and their morbidity [4–7] as well as in resistance to chemotherapy [8].”
BackgroundIshiguro, H., Akimoto, K., Nagashima, Y., Kojima, Y., Sasaki, T., Ishiguro-Imagawa, Y., Nakaigawa, N., Ohno, S., Kubota, Y., & Uemura, H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907044106 · Cited by 74
“Preoperative plasma IL-6 level is related to PSA failure after radical prostatectomy (39).”
BackgroundPersistent androgen receptor addiction in castration-resistant prostate cancer
Schweizer, M. T., & Yu, E. Y. (2015) · Journal of Hematology & Oncology · doi:10.1186/s13045-015-0225-2 · Cited by 77
“IL-6 has also been shown to associate with advanced stage prostate cancer and survival [141–144].”
BackgroundThe Emerging Role of Obesity, Diet and Lipid Metabolism in Prostate Cancer
Ferro, M., Terracciano, D., Buonerba, C., Lucarelli, G. T., Bottero, D., Perdonà, S., Riccardo Autorino, B., Serino, A., Cantiello, F., Damiano, R., et al. (2016) · Future Oncology · doi:10.2217/fon-2016-0217 · Cited by 73
Longitudinal Cytokine Expression during IMRT for Prostate Cancer and Acute Treatment Toxicity
Christensen, E. N., Pintilie, M., Evans, K., Lenarduzzi, M., Ménard, C. M., Catton, C., Diamandis, E. P., & Bristow, R. G. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0245 · Cited by 72
Pro-inflammatory cytokines and prostate-specific antigen in hyperplasia and human prostate cancer
Bouraoui, Y., Ricote, M., García‐Tuñón, I., Rodríguez‐Berriguete, G., Touffehi, M., Rais, N. B., Fraile, B., Paniagua, R., Oueslati, R., & Royuela, M. (2008) · Cancer Detection and Prevention · doi:10.1016/j.cdp.2008.02.007 · Cited by 68
Hellsten, R., Lilljebjörn, L. V., Johansson, M., Leandersson, K., & Bjartell, A. S. (2019) · The Prostate · doi:10.1002/pros.23885 · Cited by 71
“Increased levels of GM‐CSF and IL6 are observed in metastatic prostate cancer.(30,31) Galiellalactone had limited effect on prostate cancer cell–derived IL6 and VEGF, factors involved in MDSC generation, although GM‐CSF was significantly inhibited.”
Biomarkers for Evaluation of Prostate Cancer Prognosis
Esfahani, M., Ataei, N., & Panjehpour, M. (2015) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2015.16.7.2601 · Cited by 70
“It is exhibited that IL-6 acts as a paracrine and autocrine growth factor for prostate cancer cells (Shariat et al., 2001).”
BackgroundShiota, M., Yokomizo, A., & Naito, S. (2012) · Endocrine Related Cancer · doi:10.1530/erc-12-0232 · Cited by 71
“Sharifi et al. (2008) showed that the suppression of SOD2 induced the activation of AR signaling by ROS production via the following pathways.”
BackgroundInfluentialThe Present and Future of Prostate Cancer Urine Biomarkers
Rigau, M., Oliván, M., García, M., Sequeiros, T., Montes, M., Colás, E., Llauradó, M., Planas, J., de Torres, I. M., Moróte, J., et al. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140612620 · Cited by 68
“IL-6 Interleukin-6 Cytokine secreted by a variety of cell types, is involved in the immune and acute-phase response Increased concentrations of IL-6 and IL-6R in metastatic and androgen-independent PCa Diagnosis and Prognostic Blood [60–62]”
BackgroundLigand-independent activation of androgen receptors by Rho GTPase signaling in prostate cancer.
Lyons, L. S., Rao, S., Balkan, W., Faysal, J., Maiorino, C. A., & Burnstein, K. L. (2008) · Molecular Endocrinology · doi:10.1210/me.2007-0158 · Cited by 67
Molecules targeting the androgen receptor (AR) signaling axis beyond the AR‐Ligand binding domain
Elshan, N. G. R. D., Rettig, M. B., & Jung, M. E. (2018) · Medicinal Research Reviews · doi:10.1002/med.21548 · Cited by 69
“Serum levels of IL‐6 are often found to be elevated in advanced PCa patients.(111,112) Upon ligand binding to the IL‐6 receptor complex, an intracellular signaling cascade is activated where the receptor‐associated JAKs phosphorylate STAT3 at Tyr‐705.”
BackgroundBlaszczyk, N., Masri, B. A., Mawji, N. R., Ueda, T., McAlinden, G., Duncan, C. P., Bruchovsky, N., Schweikert, H.-U., Schnabel, D., Jones, E. C., et al. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-0974-3 · Cited by 66
New blood‐based biomarkers for the diagnosis, staging and prognosis of prostate cancer
Shariat, S. F., Karam, J. A., Margulis, V., & Karakiewicz, P. I. (2007) · British Journal of Urology · doi:10.1111/j.1464-410x.2007.07283.x · Cited by 64
Fen, W., Liu, Z., Xia, Y., Zhou, C., Shen, X., Li, X., Han, S.-G., Zheng, Y., Mao, Z., GONG, F.-R., et al. (2015) · Oncology Letters · doi:10.3892/ol.2015.3783 · Cited by 63
“Elevated serum concentrations of IL-6 were significantly higher in individuals with gastric, colon and prostate cancers (42,43).”
Delk, N. A., & Farach‐Carson, M. C. (2012) · Autophagy · doi:10.4161/auto.19226 · Cited by 65
Shariat, S. F., Walz, J. C., Roehrborn, C. G., Zlotta, A. R., Perrotte, P., Suardi, N. R., Fred Saad, C., & Karakiewicz, P. I. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.4669 · Cited by 63
Li, Y., Hsieh, L., Tang, R., Liao, S.-K., & Yeh, K. (2009) · Human Immunology · doi:10.1016/j.humimm.2009.01.004 · Cited by 60
A Review of the Pathophysiological Mechanisms Underlying Castration-resistant Prostate Cancer
Crowley, F., Sterpi, M., Buckley, C. W., Margetich, L., Handa, S., & Dovey, Z. (2021) · Research and Reports in Urology · doi:10.2147/rru.s264722 · Cited by 62
Fujita, K., Shimomura, M., Uemura, M., Nakata, W., Sato, M., Nagahara, A., Nakai, Y., Takamatsu, S., Miyoshi, E., & Nonomura, N. (2014) · The Prostate · doi:10.1002/pros.22824 · Cited by 58
Vibrational spectroscopy of liquid biopsies for prostate cancer diagnosis
Medipally, D., Cullen, D., Untereiner, V., Sockalingum, G. D., Maguire, A., Nguyen, T. N. Q., Bryant, J., Noone, E., Bradshaw, S., Finn, M. A., et al. (2020) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835920918499 · Cited by 58
Kulmatycki, K. M., & Jamali, F. (2005) · PubMed · Cited by 58
Cardillo, M. R., & Ippoliti, F. (2006) · PubMed · Cited by 57
Malignancy and systemic lupus erythematosus
Bernatsky, S., Clarke, A. E., & Ramsey‐Goldman, R. (2002) · Current Rheumatology Reports · doi:10.1007/s11926-002-0045-6 · Cited by 57
Cellular senescence as a possible link between prostate diseases of the ageing male
Fiard, G., Stavrinides, V., Chambers, E. S., Heavey, S., Freeman, A., Ball, R., Akbar, A. N., & Emberton, M. (2021) · Nature Reviews Urology · doi:10.1038/s41585-021-00496-8 · Cited by 58
Coutant, D. E., Kulanthaivel, P., Turner, P. K., Bell, R. L., Baldwin, J., Wijayawardana, S., Pitou, C., & Hall, S. D. (2015) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.128 · Cited by 56
Prostate cancer markers: An update
Pentyala, S., Whyard, T. C., Pentyala, S., Müller, J., Pfail, J. L., Parmar, S., Helguero, C. G., & Khan, S. (2016) · Biomedical Reports · doi:10.3892/br.2016.586 · Cited by 55
“Another study measured the plasma levels of IL-6 and IL-6 soluble receptor in 120 consecutive patients with clinically localized prostate cancer that underwent prostatectomy (44).”
Wang, L. S., Murphy, C. T., Ruth, K. J., Zaorsky, N. G., Smaldone, M. C., Sobczak, M. L., Kutikov, A., Viterbo, R., & Horwitz, E. M. (2015) · Cancer · doi:10.1002/cncr.29472 · Cited by 60
“Other obesity-related biological mechanisms include higher levels of insulin(31) and insulin-like growth factor 1,(33) leading to elevated circulating growth factors, decreased levels of testosterone, and higher levels of estrogen(34) as well as high inflammatory factors such as leptin(35) and interleukin 6.(36) Chang…”
BackgroundAdvanced prostate cancer: reinforcing the strings between inflammation and the metastatic behavior
Gueron, G., Siervi, A. D., & Vazquez, E. S. (2011) · Prostate Cancer and Prostatic Diseases · doi:10.1038/pcan.2011.64 · Cited by 52
Shen, X., Xia, Y., Lian, L., Zhou, C., Li, X., Han, S.-G., Zheng, Y., Gong, F.-R., Tao, M., Mao, Z., et al. (2016) · Oncology Letters · doi:10.3892/ol.2016.4913 · Cited by 52
“Elevated IL-6 is significantly higher in individuals with gastric cancer, as well as in patients with prostate cancer (17,18).”
Sharifi, N., Hurt, E. M., Thomas, S. B., & Farrar, W. L. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0591 · Cited by 52
Zhang, P., Wei, Q., Li, X., Wang, K., Zeng, H., Bu, H., & Li, H. (2009) · Cancer Genetics and Cytogenetics · doi:10.1016/j.cancergencyto.2009.01.017 · Cited by 50
Stromal TGF-β signaling induces AR activation in prostate cancer
Yang, F., Chen, Y., Shen, T., Guo, D., Dakhova, O., Ittmann, M., Creighton, C. J., Zhang, Y., Dang, T. D., & Rowley, D. R. (2014) · Oncotarget · doi:10.18632/oncotarget.2536 · Cited by 48
Nadiminty, N., & Gao, A. C. (2011) · World Journal of Urology · doi:10.1007/s00345-011-0771-3 · Cited by 49
“soluble IL-6 receptor have been associated with CRPC progression and are predictive of recurrence after treatment of localized cancer [50, 51].”
BackgroundPlatz, E. A., & Giovannucci, E. L. (2006) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195149616.003.0059 · Cited by 46
Corcoran, N. M., & Costello, A. J. (2003) · British Journal of Urology · doi:10.1046/j.1464-410x.2003.04025.x · Cited by 46
Pinski, J., & Dorff, T. B. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2004.12.026 · Cited by 45
Platz, E. A., Marzo, A. M. D., Erlinger, T. P., Rifai, N., Visvanathan, K., Hoffman, S. C., & Helzlsouer, K. J. (2003) · The Prostate · doi:10.1002/pros.10368 · Cited by 45
Metadata
- Authors
- Shariat, S. F., Andrews, B., Kattan, M. W., Kim, J., Wheeler, T. M., & Slawin, K. M.
- Affiliations
- Houston Methodist (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Slawin, Kevin M.
- Venue
- Urology
- Publisher
- Elsevier BV
- Published
- 2001-12
- Volume
- 58
- Issue
- 6
- Pages
- 1008-1015
- ISSN
- 0090-4295 (ISSN-L)
- OpenAlex
- W2009017218
- Cited by
- 261
- References
- 35
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 4 · 2023: 7 · 2022: 6 · 2021: 17 · 2020: 5 · 2019: 5 · 2018: 10 · 2017: 9 · 2016: 9 · 2015: 19 · 2014: 10 · 2013: 12 · 2012: 8
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Urology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1p20ca058203-01)
- National Cancer Institute (CA58203)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Urology › Prostate Cancer Diagnosis and Treatment
- Keywords
- interleukin-6, soluble IL-6 receptor, prostate cancer, bone metastasis, biochemical recurrence, radical prostatectomy, prognostic factors, Gleason score, prostate-specific antigen, tumor progression, gp130 signaling
- MeSH terms
- Adult, Aged, Analysis of Variance, Biopsy, Bone Neoplasms, Follow-Up Studies, Humans, Male, Middle Aged, Prostate, Prostatectomy, Prostatic Neoplasms, Biomarkers, Tumor, Interleukin-6, Proportional Hazards Models, Disease Progression, Receptors, Interleukin-6
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
