Inflammation amplifier, a new paradigm in cancer biology
Abstract
Tumor-associated inflammation can induce various molecules expressed from the tumors themselves or surrounding cells to create a microenvironment that potentially promotes cancer development. Inflammation, particularly chronic inflammation, is often linked to cancer development, even though its evolutionary role should impair nonself objects including tumors. The inflammation amplifier, a hyperinducer of chemokines in nonimmune cells, is the principal machinery for inflammation and is activated by the simultaneous stimulation of NF-κB and STAT3. We have redefined inflammation as local activation of the inflammation amplifier, which causes an accumulation of various immune cells followed by dysregulation of local homeostasis. Genes related to the inflammation amplifier have been genetically associated with various human inflammatory diseases. Here, we describe how cancer-associated genes, including interleukin (IL)-6, Ptgs2, ErbB1, Gas1, Serpine1, cMyc, and Vegf-α, are strongly enriched in genes related to the amplifier. The inflammation amplifier is activated by the stimulation of cytokines, such as TNF-α, IL-17, and IL-6, resulting in the subsequent expression of various target genes for chemokines and tumor-related genes like BCL2L11, CPNE7, FAS, HIF1-α, IL-1RAP, and SOD2. Thus, we conclude that inflammation does indeed associate with the development of cancer. The identified genes associated with the inflammation amplifier may thus make potential therapeutic targets of can…
Integrity signals
Registry
Cites
Statistics
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?
The IL-6 amplifier plays a key role in inflammatory diseases including cytokine storm syndromes, autoimmune diseases and cancer.
“It too plays a key role in inflammatory diseases including cytokine storm syndromes, autoimmune diseases and cancer (10, 11, 15, 41, 66–68)”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [11]
IL-6 is a major player in chronic inflammatory diseases, autoimmune diseases, cancer and cytokine storm.
“Among them, IL-6 is a major player in chronic inflammatory diseases, autoimmune diseases, cancer and cytokine storm (1, 3, 10–26).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [11]
The IL-6 Amp is related with various types of cancer, including hematologic malignancies, tumors in lung, and colorectal/intestinal, urinary/bladder/vulvar, breast, stomach and liver cancers.
“Moreover, the IL-6 Amp is related with various types of cancer, including hematologic malignancies, tumors in lung, and colorectal/intestinal, urinary/bladder/vulvar, breast, stomach and liver cancers (11).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [11]
Many cancer-associated genes were identified as regulators or target genes of the IL-6 Amp.
“Furthermore, many cancer-associated genes were identified as regulators or target genes of the IL-6 Amp (11).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [11]
Target molecules of the IL-6 Amp include EGFR, c-Myc, Pim1, VEGFα, hypoxia-inducible factor 1-alpha, MMPs and many pro-inflammatory cytokines and growth factors involved in cell survival, proliferation, angiogenesis and metastasis.
“Target molecules of the IL-6 Amp include EGFR, c-Myc, Pim1, VEGFα, hypoxia-inducible factor 1-alpha (HIF1-α), MMPs and many pro-inflammatory cytokines and growth factors involved in cell survival, proliferation, angiogenesis and metastasis (Fig. 3) (10, 11).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [11]
Cites
Autonomic nerve development contributes to prostate cancer progression
Magnon, C., Hall, S. J., Lin, J., Xue, X., Gerber, L., Freedland, S. J., & Frenette, P. S. (2013) · Science · doi:10.1126/science.1236361 · Cited by 1,287 · see citing works
A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis
Acharyya, S., Oskarsson, T., Vanharanta, S., Malladi, S., Kim, J., Morris, P. G., Manova-Todorova, K., Leversha, M., Hogg, N., Seshan, V. E., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.042 · Cited by 1,085 · see citing works
Disease-association analysis of an inflammation-related feedback loop
Murakami, M., Harada, M., Kamimura, D., Ogura, H., Okuyama, Y., Kumai, N., Okuyama, A., Singh, R., Jiang, J.-J., Atsumi, T., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.01.028 · Cited by 110 · see citing works
Self-citationMurakami, M., Okuyama, Y., Ogura, H., Asano, S., Arima, Y., Tsuruoka, M., Harada, M., Kanamoto, M., Sawa, Y., Iwakura, Y., et al. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20100900 · Cited by 100 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453 · see citing works
“Furthermore, many cancer-associated genes were identified as regulators or target genes of the IL-6 Amp (11).”
BackgroundInfluentialSelf-citationInterleukins in cancer: from biology to therapy
Briukhovetska, D., Dörr, J., Endres, S., Libby, P., Dinarello, C. A., & Kobold, S. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00363-z · Cited by 791 · see citing works
Vallée, A., & Lecarpentier, Y. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00745 · Cited by 352 · see citing works
PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation
Iwata, H., Goettsch, C., Sharma, A., Ricchiuto, P., Goh, W. W. B., Halu, A., Yamada, I., Yoshida, H., Hara, T., Wei, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms12849 · Cited by 283 · see citing works
Chronic inflammation, cancer development and immunotherapy
Wen, Y., Zhu, Y., Zhang, C., Yang, X., Gao, Y., Li, M., Yang, H., Liu, T., & Tang, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1040163 · Cited by 231 · see citing works
“…evidences demonstrate that tumorassociated inflammation could affect almost every stage of cancer: cancer development, metastasis, drug resistance and cancer recurrence by inducing genomic instability, driving selfrenewal of cancer stem-like cells (CSCs) and angiogenesis (Atsumi et al., 2014).”
BackgroundCurrent Approaches for Improving Intratumoral Accumulation and Distribution of Nanomedicines
Durymanov, M. O., Rosenkranz, A. A., & Sobolev, A. S. (2015) · Theranostics · doi:10.7150/thno.11742 · Cited by 190 · see citing works
Tanaka, K., Araki, T., Toiyama, Y., Okita, Y., Mohri, Y., & Kusunoki, M. (2016) · Springer eBooks · doi:10.1007/978-4-431-55522-3_2 · Cited by 180 · see citing works
“The molecular biology, immune pathobiology, and genetics of IBD-associated CRC are the focuses of intense research [5].”
Exosome-Derived miR-25-3p and miR-92a-3p Stimulate Liposarcoma Progression
Casadei, L., Calore, F., Creighton, C. J., Guescini, M., Batte, K., Iwenofu, O. H., Zewdu, A., Braggio, D., Bill, K. L. J., Fadda, P., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2984 · Cited by 191 · see citing works
“Cancer-related inflammation is now recognized as a tumor hallmark (29-31).”
BackgroundVitamin D Signaling in Inflammation and Cancer: Molecular Mechanisms and Therapeutic Implications
Elsharkawy, A., & Malki, A. (2020) · Molecules · doi:10.3390/molecules25143219 · Cited by 162 · see citing works
Bredholt, G., Mannelqvist, M., Stefansson, I. M., Birkeland, E., Bø, T. H., Oyan, A. M., Trovik, J., Kalland, K., Jonassen, I., Salvesen, H. B., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5344 · Cited by 163 · see citing works
“The inflammation amplifier reflect genes associated with cancer development [59], and several genes from the amplifiers were found up-regulated in necrotic tumors, like PTGS2, IL6, SERPINE1 and SOD2.”
BackgroundAndrographolide, an Anti-Inflammatory Multitarget Drug: All Roads Lead to Cellular Metabolism
Burgos, R. A., Alarcón, P., Quiroga, J., Manosalva, C., & Hancke, J. L. (2020) · Molecules · doi:10.3390/molecules26010005 · Cited by 176 · see citing works
Immune‐suppressive effects of interleukin‐6 on T‐cell‐mediated anti‐tumor immunity
Tsukamoto, H., Fujieda, K., Senju, S., Ikeda, T., Oshiumi, H., & Nishimura, Y. (2017) · Cancer Science · doi:10.1111/cas.13433 · Cited by 165 · see citing works
Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery
Zhang, B., Hu, Y., & Pang, Z. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00952 · Cited by 152 · see citing works
“As inflammation might potentially promote cancer development (Atsumi et al., 2014), local application (Seki et al.”
BackgroundInflammation triggers Zeb1-dependent escape from tumor latency
Cock, J. D., Shibue, T., Dongre, A., Keckesova, Z., Reinhardt, F., & Weinberg, R. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0608 · Cited by 143 · see citing works
“While inflammation has been shown to contribute to primary tumor progression, the role of inflammation in metastatic colonization is poorly understood (15, 16).”
BackgroundGene of the month: Interleukin 6 (IL-6)
Ataie-Kachoie, P., Pourgholami, M. H., Richardson, D. R., & Morris, D. L. (2014) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2014-202493 · Cited by 150 · see citing works
Prolyl isomerase Pin1: a promoter of cancer and a target for therapy
Chen, Y., Wu, Y., Yang, H., Li, X., Jie, M., Hu, C.-J., Wu, Y., Yang, S., & Yang, Y. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0844-y · Cited by 159 · see citing works
The role of vitamin D and VDR in carcinogenesis: Through epidemiology and basic sciences.
Merchan, B. B., Morcillo, S., Martín-Núñez, G., Tinahones, F., & Macías-González, M. (2017) · Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.11.020 · Cited by 130 · see citing works
Beug, S., Beauregard, C. E., Healy, C., Sanda, T., St-Jean, M., Chabot, J., Walker, D. E., Mohan, A. A., Earl, N., Lun, X., et al. (2017) · Nature Communications · doi:10.1038/ncomms14278 · Cited by 129 · see citing works
“We also observed a reduction in the expression of the proinflammatory cytokines IL-6 and TNF-a , which was unexpected, given that IL-17 has been previously found to stimulate the NF-k B pathway 30 .”
The prognostic significance of PD-L1 in bladder cancer.
Huang, Y.-D., Zhang, S.-D., Mccrudden, C., Chan, K. W., Lin, Y., & Kwok, H. F. (2015) · Oncology Report · doi:10.3892/or.2015.3933 · Cited by 116 · see citing works
The Impact of TRPV1 on Cancer Pathogenesis and Therapy: A Systematic Review
Li, L., Chen, C., Chiang, C., Xiao, T., Chen, Y., Zhao, Y., & Zheng, D. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.59918 · Cited by 132 · see citing works
“NF-kB and STAT3 are known to be regulators of VEGF in several cancers [161-163] and may be involved in the regulation of VEGF expression by TRPV1.”
BackgroundThe role of TLR4 in chemotherapy-driven metastasis
Ran, S. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-3525 · Cited by 113 · see citing works
“This conclusion is supported by extensive evidence showing the protective effect of the tumor environment (11), including upregulation of prosurvival proteins in tumor and tumor-associated cells.”
The triumvirate of NF-κB, inflammation and cytokine storm in COVID-19
Attiq, A., Yao, L. J., Afzal, S., & Khan, M. A. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108255 · Cited by 109 · see citing works
STAT3 and STAT5 Activation in Solid Cancers
Igelmann, S., Neubauer, H. A., & Ferbeyre, G. (2019) · Cancers · doi:10.3390/cancers11101428 · Cited by 120 · see citing works
“The coactivation of these two transcription factors amplifies pro-inflammatory gene expression driving cancer-associated inflammation [35].”
BackgroundInflammation and cancer: Till death tears them apart
Raposo, T. P., Beirão, B. C. B., Pang, L. Y., QUEIROGA, F. L., & Argyle, D. J. (2015) · The Veterinary Journal · doi:10.1016/j.tvjl.2015.04.015 · Cited by 118 · see citing works
“…receptors (Kamradt, 2013) IL-2 Interleukin-2 Tumour mitogen (Talmadge et al., 2007) IL-6 Interleukin-6 Tumour growth factor; inflammation amplifier (Atsumi et al., 2014) IL-8/CXCL8 Interleukin-8 Angiogenesis and osteolysis; promotion of migration and invasion of tumour cells (Waugh et al., 2008)…”
InfluentialInflammation, cytokines, the IL-17/IL-6/STAT3/NF-κB axis, and tumorigenesis
Zhou, S., & Chen, X. (2015) · Drug Design Development and Therapy · doi:10.2147/dddt.s86396 · Cited by 66 · see citing works
“As a result of different forms of inflammation, the tumor microenvironment contains innate immune cells, including macrophages, neutrophils, mast cells, MDSCs, dendritic cells, and NK cells and adaptive immune cells (T and B lymphocytes) in addition to the cancer cells and their surrounding stroma consisting of fibrob…”
NEDD4 Is Involved in Inflammation Development during Keloid Formation
Fujita, M., Yamamoto, Y., Jiang, J., Atsumi, T., Tanaka, Y., Ohki, T., Murao, N., Funayama, E., Hayashi, T., Osawa, M., et al. (2018) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2018.07.044 · Cited by 93 · see citing works
Self-citationTzeng, H., Chyuan, I., & Lai, J. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114760 · Cited by 81 · see citing works
Nanoparticle-based drug delivery systems in cancer: A focus on inflammatory pathways
Afshari, A. R., Sanati, M., Mollazadeh, H., Kesharwani, P., Johnston, T. P., & Sahebkar, A. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.01.008 · Cited by 87 · see citing works
Role of Chemokines in Thyroid Cancer Microenvironment: Is CXCL8 the Main Player?
Rotondi, M., Coperchini, F., Latrofa, F., & Chiovato, L. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00314 · Cited by 77 · see citing works
“Am J Clin Pathol (1988) 89(3):295–300.”
BackgroundInfluentialPolycystic ovary syndrome and circulating inflammatory markers
Zangeneh, F. Z., Naghizadeh, M., & Masoumi, M. (2017) · International Journal of Reproductive BioMedicine · doi:10.29252/ijrm.15.6.375 · Cited by 77 · see citing works
Temporal Expression of Growth Factors Triggered by Epiregulin Regulates Inflammation Development
Harada, M., Kamimura, D., Arima, Y., Kohsaka, H., Nakatsuji, Y., Nishida, M., Atsumi, T., Meng, J., Bando, H., Singh, R., et al. (2015) · Journal of Immunology · doi:10.4049/jimmunol.1400562 · Cited by 72 · see citing works
“I nterleukin-6 is a cytokine expressed by various activated cells, including CD4 cells, and has an important role in the development of inflammation (1, 2).”
BackgroundSelf-citationMacrophages in tumor: An inflammatory perspective
Goswami, K. K., Bose, A., & Baral, R. (2021) · Clinical Immunology · doi:10.1016/j.clim.2021.108875 · Cited by 86 · see citing works
Arima, Y., Kamimura, D., Atsumi, T., Harada, M., Kawamoto, T., Nishikawa, N., Stofkova, A., Ohki, T., Higuchi, K., Morimoto, Y., et al. (2015) · eLife · doi:10.7554/elife.08733 · Cited by 66 · see citing works
“Activation of the inflammation amplifier is associated with many human diseases and disorders such as autoimmune and neurodegenerative diseases including MS ( Murakami et al., 2013 ; Atsumi et al., 2014 ).”
BackgroundInfluentialSelf-citationImpact of the N-Terminal Domain of STAT3 in STAT3-Dependent Transcriptional Activity
Hu, T., Yeh, J. E., Pinello, L., Jacob, J., Chakravarthy, S., Yuan, G.-C., Chopra, R., & Frank, D. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00060-15 · Cited by 60 · see citing works
“Ni has been reported to 606 activate inflammatory transcription factors like NF-κB (74), while metal ions have been shown 607 to directly regulate STAT3 (31-33), another established pro-inflammation factor (75).”
BackgroundPossible cancer-causing capacity of COVID-19: Is SARS-CoV-2 an oncogenic agent?
Jahankhani, K., Ahangari, F., Adcock, I., & Mortaz, E. (2023) · Biochimie · doi:10.1016/j.biochi.2023.05.014 · Cited by 59 · see citing works
Wang, W., Wu, D.-G., He, X.-T., Hu, X.-T., Hu, C.-W., Shen, Z., Lin, J.-T., Pan, Z.-H., He, Z., Lin, H., et al. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.06.009 · Cited by 58
Schwartz, B., & Hadar, Y. (2014) · Annals of Translational Medicine · doi:10.3978/j.issn.2305-5839.2014.01.03 · Cited by 57
“In general, β-[1,3]-D-glucans with β-[1,6] linkages have a high molecular weight (over 2,000 kDa), high viscosity and low water solubility.”
BackgroundMucin 2 silencing promotes colon cancer metastasis through interleukin-6 signaling
Hsu, H.-P., Lai, M., Lee, J.-C., Yen, M., Weng, T.-Y., Chen, W.-C., Fang, J.-H., & Chen, Y.-L. (2017) · Scientific Reports · doi:10.1038/s41598-017-04952-7 · Cited by 56
Mechanistic Insights of Vitamin D Anticancer Effects.
Ma, Y.-Y., Johnson, C. S., & Trump, D. (2016) · Vitamins and hormones · doi:10.1016/bs.vh.2015.11.003 · Cited by 55 · see citing works
Interleukin-6 induces drug resistance in renal cell carcinoma.
Ishibashi, K., Koguchi, T., Matsuoka, K., Onagi, A., Tanji, R., Takinami-Honda, R., Hoshi, S., Onoda, M., Kurimura, Y., Hata, J., et al. (2018) · Fukushima Journal of Medical Science · doi:10.5387/fms.2018-15 · Cited by 53 · see citing works
Živančević-Simonović, S., Mihaljević, O., Majstorović, I., Popović, S., Markovic, S., Milošević-Djordjević, O., Jovanović, Z., Mijatovic-Teodorovic, L., Mihajlović, D., & Čolić, M. (2015) · Cancer Immunology and Immunotherapy · doi:10.1007/s00262-015-1705-5 · Cited by 51
Yoshida, N., Kinugasa, T., Miyoshi, H., Sato, K., Yuge, K., Ohchi, T., Fujino, S., Shiraiwa, S., Katagiri, M., Akagi, Y., et al. (2016) · Annals of Surgical Oncology · doi:10.1245/s10434-015-4923-3 · Cited by 49 · see citing works
Illeperuma, R., Kim, D. K., Park, Y. J., Son, H., Kim, J.-Y., Kim, J., Lee, D. Y., Kim, K.-Y., Jung, D., Tilakaratne, W., et al. (2015) · International Journal of Cancer · doi:10.1002/ijc.29636 · Cited by 48 · see citing works
Targeting of stress response pathways in the prevention and treatment of cancer
Zelenka, J., Koncošová, M., & Ruml, T. (2018) · Biotechnology Advances · doi:10.1016/j.biotechadv.2018.01.007 · Cited by 50 · see citing works
Commonalities in the Association between PPARG and Vitamin D Related with Obesity and Carcinogenesis
Bandera-Merchán, B., Tinahones, F. J., & Macías‐González, M. (2016) · PPAR Research · doi:10.1155/2016/2308249 · Cited by 50 · see citing works
“Vitamin D has been extensively associated with antiinflammatory actions [141–143], apoptotic mechanisms [144– 150], antiproliferative functions [151–159], prodifferentiation effects [160–166], antiangiogenic properties [167–171], a potential role-managing invasion and metastasis [172–184], microRNA…”
BackgroundZhang, Q., Chai, S., Wang, W., Wan, C., Zhang, F., Li, Y., & Wang, F.-C. (2018) · Oncology Letters · doi:10.3892/ol.2018.9703 · Cited by 42 · see citing works
“Evidence indicates that gastric epithelial cells that were exposed to inflammatory microenvironment in the long term could induce neoplastic transformation (3,4).”
BackgroundXu, Y.-H., Li, Z.-L., & Qiu, S.-F. (2018) · Translational Oncology · doi:10.1016/j.tranon.2017.11.008 · Cited by 42
Yi, L., Shen, H.-T., Zhao, M., Shao, P., Liu, C.-P., Cui, J.-F., Wang, J., Wang, C., Guo, N., Kang, L., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-08537-2 · Cited by 42
DEPDC1 is required for cell cycle progression and motility in nasopharyngeal carcinoma
Feng, X.-F., Zhang, C.-D., Zhu, L., Zhang, L., Li, H.-X., He, L.-X., Mi, Y., Wang, Y.-T., Zhu, J., & Bu, Y. (2017) · OncoTarget · doi:10.18632/oncotarget.18868 · Cited by 42
“It is well known that NF-κB pathway plays a critical role in tumorgenesis and metastasis as well as inflammatory diseases, and serves as an effective target for the treatment of various cancers [22, 23, 25].”
BackgroundBuas, M. F., He, Q., Johnson, L. G., Onstad, L., Levine, D., Thrift, A., Gharahkhani, P., Palles, C., Lagergren, J., Fitzgerald, R., et al. (2016) · Gut · doi:10.1136/gutjnl-2016-311622 · Cited by 42 · see citing works
LLL12, a novel small inhibitor targeting STAT3 for hepatocellular carcinoma therapy
Zuo, M., Li, C.-L., Lin, J., & Javle, M. (2015) · OncoTarget · doi:10.18632/oncotarget.3458 · Cited by 41 · see citing works
“Also, most proinflammatory agents have been shown to activate STAT3 [7, 8].”
BackgroundSalmiheimo, A., Mustonen, H., Stenman, U., Puolakkainen, P., Kemppainen, E., Seppänen, H., & Haglund, C. (2016) · PLoS ONE · doi:10.1371/journal.pone.0163064 · Cited by 40
JAK-STAT Signaling in Autoimmunity and Cancer
Parveen, S., Fatma, M., Mir, S. S., Dermime, S., & Shahab Uddin, M. S. (2025) · ImmunoTargets and Therapy · doi:10.2147/itt.s485670 · Cited by 51 · see citing works
“The intricacy has prompted a growing number of research investigations focused on elucidating the specific mechanisms by which JAK/STAT signaling contributes to these diseases and identifying possible therapeutic targets within this pathway (Figure 3).”
Francescangeli, F., Angelis, M. L. D., Baiocchi, M., Rossi, R., Biffoni, M., & Zeuner, A. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.592891 · Cited by 40 · see citing works
“During SARS-CoV-2 infection IL-6 signaling is activated in both immune and non-immune cells triggering the so-called IL-6 inflammation amplifier, a positive feedback loop resulting in the production of additional IL-6, of VEGF and of multiple chemoattractant proteins (35) (Figure 1).”
BackgroundWang, Y., Li, J., Wang, Y.-Q., & Miao, Z. (2015) · Oncotarget · doi:10.18632/oncotarget.3648 · Cited by 45 · see citing works
Yang, T.-T., Zhang, X., Wang, M., Zhang, J., Huang, F., Cai, J., Zhang, Q., Mao, F., Zhu, W., Qian, H., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097569 · Cited by 39 · see citing works
“During the past decades, the link of inflammation to cancer has attracted a lot of attention [5,6].”
BackgroundModulation of CD4 T Cell Response According to Tumor Cytokine Microenvironment
Accogli, T., Bruchard, M., & Végran, F. (2021) · Cancers · doi:10.3390/cancers13030373 · Cited by 39 · see citing works
“Induction of this pathway is responsible for T cell proliferation and commitment to the Th17 and Tfh subtypes [99,100].”
BackgroundLan, M., Lü, W., Zou, T., Li, L., Liu, F., Cai, T., & Cai, Y. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03696-4 · Cited by 39 · see citing works
Meseure, D., Alsibai, K. D., & Nicolas, A. (2014) · Cancer Microenvironment · doi:10.1007/s12307-014-0158-2 · Cited by 35 · see citing works
Overriding TKI resistance of renal cell carcinoma by combination therapy with IL-6 receptor blockade
Ishibashi, K., Haber, T., Breuksch, I., Gebhard, S., Sugino, T., Kubo, H., Hata, J., Koguchi, T., Yabe, M., Kataoka, M., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.19420 · Cited by 55 · see citing works
“NFκB-triggered positive feedback for IL-6 signaling, also known as inflammation amplifier, induces various molecules to create a microenvironment which promotes cancer development [40].”
BackgroundArabzadeh, S., Hossein, G., Salehi-Dulabi, Z., & Zarnani, A. (2016) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-016-0003-3 · Cited by 36
“It is well known that inflammation mediates cancer cell migration [3].”
BackgroundInfluentialKumar, M. M., Davuluri, S., Poojar, S., Mukherjee, G., Bajpai, A., Bafna, U., Devi, U., Kallur, P. P. R., Kshitish, A. K., & Jayshree, R. S. (2016) · Tumor Biology · doi:10.1007/s13277-015-4257-6 · Cited by 36 · see citing works
Huang, Y.-H., Cai, T.-G., Xia, X., Cai, Y., & Wu, X.-Y. (2016) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.18433/j3sg7k · Cited by 36 · see citing works
“TNF-α is an inflammatory cytokine with a variety of biological activities (30) that participates in the activation of immune response, mediation of systemic inflammation, and induction of tumorigenesis.”
BackgroundDiterpenoids from the seeds of Euphorbia lathyris and their anti-inflammatory activity.
Wang, Y.-L., Song, Z., Guo, Y.-Y., Xie, H.-D., Zhang, Z., Sun, D.-J., Li, H., & Chen, L.-X. (2021) · Bioorganic chemistry (Print) · doi:10.1016/j.bioorg.2021.104944 · Cited by 35
Inflammatory pathway interactions and cancer multidrug resistance regulation.
Mirzaei, S. A., Dinmohammadi, F., Alizadeh, A., & Elahian, F. (2019) · Life Science · doi:10.1016/j.lfs.2019.116825 · Cited by 35 · see citing works
Cheon, S. Y., Kim, J., Kam, E. H., Ho, C.-C., Kim, E. J., Chung, S., Jeong, J., Lee, D. D.-H., Lee, S., & Koo, B. (2017) · Scientific Reports · doi:10.1038/s41598-017-14027-2 · Cited by 34 · see citing works
Macha, M., Krishn, S., Jahan, R., Banerjee, K., Batra, S., & Jain, M. (2015) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2015.01.001 · Cited by 35 · see citing works
“Activation of several transcription factors like NF-jB, HIF-1b, and STAT3 [52] during neoplastic transformation induces expression of pro-inflammatory cytokines, chemokines, prostaglandins and nitric oxide in both tumor and stromal cells and create a tumor promoting inflammatory microenvironment [53].”
A Higher Frequency of CD14+CD169+ Monocytes/Macrophages in Patients with Colorectal Cancer
Li, C., Luo, X., Lin, Y., Tang, X., Ling, L., Wang, L., & Jiang, Y.-F. (2015) · PLoS ONE · doi:10.1371/journal.pone.0141817 · Cited by 34 · see citing works
Evaluation of a New Survivin ELISA and UBC® Rapid for the Detection of Bladder Cancer in Urine
Gleichenhagen, J., Arndt, C., Casjens, S., Meinig, C., Gerullis, H., Raiko, I., Brüning, T., Ecke, T., & Johnen, G. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010226 · Cited by 32
“A limitation of the markers that has been reported before is the reduced performance associated with other urologic diseases, confounders that would also be expected in a typical clinical setting [45,50,55,56].”
BackgroundRbm10 regulates inflammation development via alternative splicing of Dnmt3b
Atsumi, T., Suzuki, H., Jiang, J., Okuyama, Y., Nakagawa, I., Ota, M., Tanaka, Y., Ohki, T., Katsunuma, K., Nakajima, K., et al. (2017) · International Immunology · doi:10.1093/intimm/dxx067 · Cited by 41 · see citing works
Self-citationHead-to-Head Comparison of Anti-Inflammatory Performance of Known Natural Products In Vitro
Allijn, I. E., Vaessen, S., van Ufford, L. Q., Beukelman, K., de Winther, M., Storm, G., & Schiffelers, R. (2016) · PLoS ONE · doi:10.1371/journal.pone.0155325 · Cited by 32 · see citing works
“Uncontrolled inflammation is underlying most chronic diseases such as cardiovascular disease, arthritis, asthma and type 2 diabetes mellitus [1] and is often linked to cancer development [1,2].”
BackgroundTakada, Y., Kamimura, D., Jiang, J.-J., Higuchi, H., Iwami, D., Hotta, K., Tanaka, Y., Ota, M., Higuchi, M., Nishio, S., et al. (2020) · International Immunology · doi:10.1093/intimm/dxaa032 · Cited by 31 · see citing works
Self-citationChronic inflammation-related DNA damage response: a driving force of gastric cardia carcinogenesis
Lin, R.-H., Xiao, D.-J., Guo, Y., Tian, D.-P., Yun, H., Chen, D., & Su, M. (2014) · OncoTarget · doi:10.18632/oncotarget.3091 · Cited by 31
“Clinical epidemiological studies revealed that over 15%-20% of all solid tumors may be related to chronic inflammation [12-15].”
BackgroundSabharwal, L., Kamimura, D., Meng, J., Bando, H., Ogura, H., Nakayama, C., Jiang, J., Kumai, N., Suzuki, H., Atsumi, T., et al. (2014) · The Journal of Biochemistry · doi:10.1093/jb/mvu057 · Cited by 34 · see citing works
“In addition, genes genetically linked with neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis were also significantly enriched in the gene lists (27, 28), suggesting that the inflammation amplifier contributes to the pathogenesis of these neuroinflammatory dis…”
BackgroundSelf-citationAdvances in research on the interaction between inflammation and cancer
Song, X.-D., Wang, Y.-N., Zhang, A., & Liu, B. (2019) · Journal of International Medical Research · doi:10.1177/0300060519895347 · Cited by 30
“In particular, some cytokines activate the NF-jB and STAT family of transcription factors, which in turn link the inflammatory environment, tumours and immune cells with other components of the tumour ‘secreting proteome’ and directly control TME by regulating survival factors.(61) Taking IL-6 as an example, its effec…”
BackgroundŠtofková, A., Kamimura, D., Ohki, T., Ota, M., Arima, Y., & Murakami, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-38895-y · Cited by 35 · see citing works
Self-citationHuseby, E. S., Kamimura, D., Arima, Y., Parello, C. S. L., Sasaki, K., & Murakami, M. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00295 · Cited by 25 · see citing works
“We termed this synergistic effect the inflammation amplifier (Atsumi et al., 2014).”
BackgroundSelf-citationXu, Y., Sun, D., Xiong, L., Zhang, Z., Li, Y., Li, H., Li, H., & Chen, L. (2024) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2024.107190 · Cited by 27 · see citing works
Yang, C., Sun, S., Zhang, Q., Guo, J., Wu, T., Liu, Y., Yang, M., Zhang, Y., & Peng, Y. (2020) · Stem Cells International · doi:10.1155/2020/2134565 · Cited by 35 · see citing works
“Inflammation amplifiers play key roles in the development and progression of various human diseases, including autoimmune, neurodegenerative, and other inflammatory diseases [35].”
BackgroundOta, M., Tanaka, Y., Nakagawa, I., Jiang, J.-J., Arima, Y., Kamimura, D., Onodera, T., Iwasaki, N., & Murakami, M. (2019) · Arthritis & Rheumatology · doi:10.1002/art.41182 · Cited by 28 · see citing works
“As a key molecular mechanism in chronic inflammation, we have previously reported on the topic of the interleukin6 (IL6) amplifier (13,14).”
BackgroundSelf-citationA critical role of mir-199a in the cell biological behaviors of colorectal cancer
Ye, H., Pang, L.-P., Wu, Q., Zhu, Y.-Z., Guo, C., Deng, Y., & Zheng, X. (2015) · Diagnostic Pathology · doi:10.1186/s13000-015-0260-x · Cited by 28 · see citing works
“In advance, HIF-1α is reported to be involved in kinds of progresses of tumorigenesis including proliferation, angiogenesis, metastasis, and chemotherapy resistance [5].”
BackgroundBidirectional communication between neural and immune systems
Kamimura, D., Tanaka, Y., Hasebe, R., & Murakami, M. (2019) · International Immunology · doi:10.1093/intimm/dxz083 · Cited by 40 · see citing works
Self-citationELKAHLOUN, A. G., Rodríguez, Y., Alaiyed, S., Wenzel, E. D., & Saavedra, J. M. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1300-9 · Cited by 30 · see citing works
“cer is not surprising, since inflammation has been earlier characterized as a major factor in the development and progression of malignancies [89, 90].”
Meseure, D., Vacher, S., Alsibai, K. D., Trassard, M., Nicolas, A., Leclère, R., Lerebours, F., Guinebretière, J., Marangoni, E., Lidereau, R., et al. (2016) · Cancer Microenvironment · doi:10.1007/s12307-016-0186-1 · Cited by 27
“TLRs are actually considered as major actors implicated in chronic inflammatory-driven carcinogenesis [28, 29].”
BackgroundResultShan, Y., Hsu, H.-P., Lai, M., Yen, M., Fang, J.-H., Weng, T.-Y., & Chen, Y.-L. (2014) · Oncology Report · doi:10.3892/or.2014.3544 · Cited by 27 · see citing works
“IL-6 can also regulate the immune microenvironment surrounding the tumor (14).”
BackgroundAdvances in nuclei targeted delivery of nanoparticles for the management of cancer
Goyal, P., & Malviya, R. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188881 · Cited by 33 · see citing works
IL-1RAP, a Key Therapeutic Target in Cancer
Frenay, J., Bellaye, P., Oudot, A., Helbling, A., Petitot, C., Ferrand, C., Collin, B., & Dias, A. M. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314918 · Cited by 29 · see citing works
“In this context, numerous cytokines and their pathways are broadly over-expressed among the different kinds of cancer, representing potential therapeutic targets [10,17,18].”
BackgroundProliferative Pathways of Vascular Smooth Muscle Cells in Response to Intermittent Hypoxia
Kyotani, Y., Takasawa, S., & Yoshizumi, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112706 · Cited by 24 · see citing works
“This is consistent with the previously proposed paradigm that activation of inflammation amplifiers is associated with the development of various tumors [105].”
Liu, Y., Zhang, Z., Han, D., Zhao, Y., Yan, X., & Cui, S. (2022) · Frontiers in Public Health · doi:10.3389/fpubh.2022.980987 · Cited by 30 · see citing works
Cao, J., Yang, X., Xiong, L., Wu, M., Chen, S., Xu, H., Gong, Y., Zhang, L., Zhang, Q., & Zhang, X. L. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.990469 · Cited by 24 · see citing works
“The IL6 amplifier (IL6 Amp) is an amplification mechanism, the synergistic interaction of STAT3 with nuclear factor-κB (NF-κB) produces IL6 and various other cytokines and chemokines (Hirano, 2010; Murakami et al., 2013; Atsumi et al., 2014).”
BackgroundPharmacological Potential of Lathyrane-Type Diterpenoids from Phytochemical Sources
Vela, F., Ezzanad, A., Hunter, A., Macías-Sánchez, A., & Hernández-Galán, R. (2022) · Pharmaceuticals · doi:10.3390/ph15070780 · Cited by 25 · see citing works
“Inflammation is considered to be the body’s normal response to defend itself against pathogens and injuries, but excessive inflammation can affect the normal function of tissues and organs, leading to chronic diseases and sometimes the development of cancer [60,61].”
BackgroundJiang, X., Wang, J., Chen, X.-J., Hong, Y., Wu, T., Chen, X.-B., Xia, J., & Cheng, B. (2016) · OncoTarget · doi:10.18632/oncotarget.7585 · Cited by 25 · see citing works
Oliveira, H., Cai, X.-S., Zhang, Q., de Freitas, V. D., Mateus, N., He, J.-R., & Fernandes, I. (2017) · Food & Function · doi:10.1039/c7fo00091j · Cited by 24 · see citing works
“TRP inflammation” relationship in cardiovascular system
Numata, T., Takahashi, K., & Inoue, R. (2015) · Seminars in Immunopathology · doi:10.1007/s00281-015-0536-y · Cited by 23 · see citing works
“Under these pathological conditions, the activation of transcription factors, e.g., NF-κB, nuclear factor of activated T cell (NFAT), STAT3, and HIF-1, by inflammatory cytokines appears crucial for the amplification loop of inflammasomes [94] [95] [96] [97] .”
BackgroundYan, J., & Huang, J. (2014) · Oncoimmunology · doi:10.4161/21624011.2014.953423 · Cited by 24 · see citing works
“These tumor cells can secrete inflammatory cytokines, chemokines, metabolites, and other tumor-promoting molecules such as prostaglandin E2 (PGE2), matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF).(2) Among these, the cytokine IL-17 has recently drawn more attention due to its role in tu…”
BackgroundLiu, P., Jia, S., Lou, Y., He, K., & Xu, L. X. (2019) · International Journal of Hyperthermia · doi:10.1080/02656736.2019.1579373 · Cited by 24 · see citing works
“Acute inflammation caused by physical, chemical injury or an infectious agent can initiate an inflammatory cascade to help activation of innate and adaptive immunity [4], and skew the immune response toward Th1 type immunity, which is a characteristic of immune cell-mediated cytotoxic killing [5,6].”
BackgroundCho, Y., Kim, C. H., Ha, T., & Ahn, H. (2016) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2015-0150 · Cited by 23
Interlinking pathways: a narrative review on the role of IL-6 in cancer and atherosclerosis
Cau, R., & Saba, L. (2023) · Cardiovascular Diagnosis and Therapy · doi:10.21037/cdt-24-344 · Cited by 22 · see citing works
“In particular, classical IL-6 signaling is regarded as crucial for maintaining homeostatic processes, while trans-signaling has been shown to specifically amplify inflammation and promote inflammation-induced carcinogenesis (18,45).”
Diterpenoids with anti-inflammatory activity from Euphorbia wallichii.
Wang, Y.-L., Sun, D.-J., Jiang, Q.-H., Xiong, L., Zhang, N., Li, H., & Chen, L.-X. (2022) · Phytochemistry · doi:10.1016/j.phytochem.2022.113486 · Cited by 22 · see citing works
Breakpoint Cluster Region–Mediated Inflammation Is Dependent on Casein Kinase II
Meng, J., Jiang, J.-J., Atsumi, T., Bando, H., Okuyama, Y., Sabharwal, L., Nakagawa, I., Higuchi, H., Ota, M., Okawara, M., et al. (2016) · Journal of Immunology · doi:10.4049/jimmunol.1601082 · Cited by 22 · see citing works
“The main functional molecules of the inflammation amplifier are chemokines and growth factors, which deregulate local homeostasis via an accumulation of various immune cells and proliferate various regional cells, whereas IL-6 mainly acts as fuel to maintain the activation of STAT3 (16, 17).”
BackgroundInfluentialSelf-citation
- Authors
- Atsumi, T., Singh, R., Sabharwal, L., Bando, H., Meng, J., Arima, Y., Yamada, M., Harada, M., Jiang, J.-J., Kamimura, D., Ogura, H., Hirano, T., & Murakami, M.
- Affiliations
- Japan Science and Technology Agency (JP)
- ORCID
- Venue
- Cancer Research
- Published
- 2014-01-01
- Volume
- 74
- Issue
- 1
- Pages
- 8-14
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2101899879
- Cited by
- 217
- References
- 0
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 18 · 2023: 13 · 2022: 16 · 2021: 14 · 2020: 12 · 2019: 18 · 2018: 18 · 2017: 20 · 2016: 20 · 2015: 33 · 2014: 14 · 2013: 1
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (24790472, 24249028, 26460574, 24390098)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- tumor inflammation, chronic inflammation, carcinogenesis, NF-κB, STAT3, tumor microenvironment, cytokines, interleukin-6, cyclooxygenase-2, EGF receptor, GAS1, SERPINE1, c-Myc, VEGFα, HIF-1α, therapeutic target
- MeSH terms
- Animals, Humans, Inflammation, Neoplasms, Signal Transduction, Tumor Microenvironment
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
