Prognostic significance of Hypoxia-Inducible Factor 1 alpha(HIF-1alpha) expression in serous ovarian cancer: an immunohistochemical study
Open accessAbstract
BACKGROUND: The hypoxia-inducible factor (HIF) has emerged as an attractive target for cancer therapy. The few publications addressing the prognostic significance of Hypoxia-Inducible Factor 1 alpha (HIF-1 alpha) cellular expression in ovarian cancer produced contradictory findings which are not permissible to widely acceptable conclusions and clinical applications. Our study was designed to investigate this by including a comparatively large number of cases and by using a combination of antibodies to analyze immunohistochemically the expression of HIF-1 alpha. METHODS: One hundred (n = 100) neoplastic and 20 benign (controls) pathological samples from paraffin-embedded tissue were included. They were classified after surgery as stage I (n = 23) and stage III G3 (n = 55). Also 22 borderline serous adenocarcinoma patients and 20 benign controls were stained. The mean follow up was 3 years. Only patients with the diagnosis of serous carcinoma of stage III, G3 who received 6 cycles of postoperative TC (175-180 mg/m2 paclitaxel and carboplatin after calculating the area under the concentration curve) with complete medical records (n = 55) were selected for survival analysis. The survival analysis of the samples compared two groups after the patients were dichotomized by HIF-1 alpha final score to positive and negative. RESULTS: The frequency of the nuclear expression of HIF-1 alpha in benign tumours was significantly lower (median: no expression) than in borderline and ovarian cancer tumours combined (p < 0.001). HIF-1 alpha expression in serous ovarian carcinoma was not stage dependent. The overall survival of patients with tumours that stained strongly for HIF-1 alpha was significantly shorter than that of patients with tumours that stained weakly or were negative for HIF-1 alpha (p = 0.01). Kaplan-Meier survival curves confirmed that HIF-1 alpha "positive" had decreased overall survival compared to HIF-1 alpha "negative" patients (p = 0.003) and this was an independent adverse prognostic factor (multivariable analysis p = 0.006). HIF-1 alpha "positive" patients displayed a shorter median progress free interval (PFI) (not statistically significant p > 0.05). Interestingly the overall PFI of the subgroup of patients that have undergone suboptimal cytoreduction at primary surgery (n = 21) with tumours that stained strongly for HIF-1 alpha was significantly worse than that of patients with tumours that stained weakly or were negative for HIF- 1 alpha (p = 0.03). CONCLUSION: Our report confirms the prognostic value of HIF-1 alpha when restricted to poorly differentiated serous ovarian carcinoma. In addition it shows that this association is elusive, since it is not only methodology-related but it can be antibody-depended. There is adequate evidence to speculate that targeting HIF-1 alpha could improve the long-term prognosis of these patients In order to increase the overall sensitivity of the immunoassay, maintaining acceptable levels of specificity, a panel of antibodies should be used.
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HIF-1α protein is overexpressed in various common solid malignant tumors including breast, colon, gastric, lung, skin, ovarian, pancreatic, prostate, and renal carcinomas compared to their respective normal tissues.
“The HIF-1α protein is overexpressed in various common solid malignant tumors including breast, colon, gastric, lung, skin, ovarian, pancreatic, prostate, and renal carcinomas compared to their respective normal tissues.”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Daponte et al., 2008
The Results (page unavailable) report HIF-1α protein expression in 60% of cancerous ovarian samples versus 14% of non-cancerous ovarian samples. The Discussion says expression has been noted in many tumor types, but our copy does not establish overexpression relative to normal tissue for the other eight named carcinomas. (LLM, conf=0.90)
Experimental — accuracy not yet measuredMany benign tumors show very little or no HIF-1α expression.
“In contrast, many benign tumors show very little or no HIF-1α expression (Zhong et al., 1999;Daponte et al., 2008;Simiantonaki et al., 2008;Mayer et al., 2008b).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Daponte et al., 2008
Wenger et al. found that the suppressive effects of carboplatin and etoposide on mouse embryonic fibroblast proliferation were significantly increased when HIF-1α was deactivated.
“Notably, Wenger et al. examined the impact of hypoxia on mouse embryonic fibroblast proliferation, and found that the suppressive effects of agents like carboplatin and etoposide on cell growth were significantly increased when HIF-1α was deactivated.296”
From Drug repurposing for cancer therapy (2024) · cites this paper as [296]
The Discussion links HIF-1α and hypoxia to possible chemoresistance in ovarian tumours, but does not report the claimed mouse embryonic fibroblast experiment. Searches for fibroblasts, carboplatin, etoposide, and HIF-1α deactivation found no passage describing that result; the References list Wenger works but do not establish this finding. (LLM, conf=0.76)
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Cites
Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717 · see citing works
(1999) · PubMed · Cited by 2,204 · see citing works
Regulation of Mammalian O <sub>2</sub> Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914 · see citing works
Talks, K. L., Turley, H., Gatter, K. C., Maxwell, P. H., Pugh, C. W., Ratcliffe, P. J., & Harris, A. L. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64554-3 · Cited by 1,312 · see citing works
Integration of Oxygen Signaling at the Consensus HRE
Wenger, R. H., Stiehl, D. P., & Camenisch, G. (2005) · Science's STKE · doi:10.1126/stke.3062005re12 · Cited by 1,032 · see citing works
2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF
Mabjeesh, N. J., Escuin, D., LaVallee, T. M., Pribluda, V. S., Swartz, G. M., Johnson, M. S., Willard, M. T., Zhong, H., Simons, J. W., & Giannakakou, P. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00077-1 · Cited by 730 · see citing works
Kallio, P., Okamoto, K., O'Brien, S., Carrero, P., Makino, Y., Tanaka, H., & Poellinger, L. (1998) · EMBO Journal · doi:10.1093/emboj/17.22.6573 · Cited by 707 · see citing works
Expression of hypoxia-inducible factor 1? in brain tumors
Zagzag, D., Zhong, H., Scalzitti, J. M., Laughner, E., Simons, J. W., & Semenza, G. L. (2000) · Cancer · doi:10.1002/1097-0142(20000601)88:11 · Cited by 603 · see citing works
Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies
Shannon, A. M., Bouchier-Hayes, D. J., Condron, C. M., & Toomey, D. (2003) · Cancer Treatment Reviews · doi:10.1016/s0305-7372(03)00003-3 · Cited by 559 · see citing works
Birner, P., Schindl, M., Obermair, A., Breitenecker, G., & Oberhuber, G. (2001) · PubMed · Cited by 310 · see citing works
(2002) · PubMed · Cited by 296 · see citing works
Koukourakis, M. I., Bentzen, S. M., Giatromanolaki, A., Wilson, G. D., Daley, F. M., Saunders, M. I., Dische, S., Sivridis, E., & Harris, A. L. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.7474 · Cited by 289 · see citing works
Koukourakis, M. I., Giatromanolaki, A. N., Skarlatos, J., Corti, L., Blandamura, S., Piazza, M., Gatter, K. C., & Harris, A. L. (2001) · PubMed · Cited by 274 · see citing works
Mylonis, I., Chachami, G., Samiotaki, M. K., Panayotou, G., Paraskeva, E., Kalousi, A., Georgatsou, E., Bonanou, S., & Simos, G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605058200 · Cited by 266 · see citing works
Self-citationGenerali, D., Berruti, A., Brizzi, M. P., Campo, L., Bonardi, S., Wigfield, S., Bersiga, A., Allevi, G., Milani, M., Aguggini, S., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2690 · Cited by 250 · see citing works
Statistics for Health Professionals
Shott, S. (1991) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-199102000-00029 · Cited by 240 · see citing works
Escuín, D., Kline, E. R., & Giannakakou, P. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4095 · Cited by 183 · see citing works
RAD001 (Everolimus) Delays Tumor Onset and Progression in a Transgenic Mouse Model of Ovarian Cancer
Mabuchi, S., Altomare, D. A., Connolly, D. C., Klein–Szanto, A. J., Litwin, S., Hoelzle, M. K., Hensley, H. H., Hamilton, T. C., & Testa, J. R. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4490 · Cited by 181 · see citing works
Inhibiting Hypoxia-Inducible Factor 1 for Cancer Therapy
Melillo, G. (2006) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-06-0235 · Cited by 165 · see citing works
Ricker, J. L., Chen, Z., Yang, X. P., Pribluda, V. S., Swartz, G. M., & Waes, C. V. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-1393 · Cited by 129 · see citing works
Osada, R., Horiuchi, A., Kikuchi, N., Yoshida, J., Hayashi, A., Ota, M., Katsuyama, Y., Mellilo, G., & Konishi, I. (2007) · Human Pathology · doi:10.1016/j.humpath.2007.02.010 · Cited by 120 · see citing works
VEGF and HIF-1α expression are increased in advanced stages of epithelial ovarian cancer
Wong, C., Wellman, T. L., & Lounsbury, K. M. (2003) · Gynecologic Oncology · doi:10.1016/j.ygyno.2003.08.022 · Cited by 111 · see citing works
Statistics for health professionals
Kirchhoff, K. T. (1991) · Journal of Professional Nursing · doi:10.1016/8755-7223(91)90080-5 · Cited by 110 · see citing works
Treeck, O., Wackwitz, B., Haus, U., & Ortmann, O. (2006) · Gynecologic Oncology · doi:10.1016/j.ygyno.2005.12.019 · Cited by 96 · see citing works
Chaperoning Oncogenes: Hsp90 as a Target of Geldanamycin
Neckers, L. (2005) · Handbook of experimental pharmacology · doi:10.1007/3-540-29717-0_11 · Cited by 79 · see citing works
Using Natural Product Inhibitors to Validate Hsp90 as a Molecular Target in Cancer
Neckers, L. (2006) · Current Topics in Medicinal Chemistry · doi:10.2174/156802606777811979 · Cited by 75 · see citing works
A dominant-negative isoform lacking exons 11 and 12 of the human hypoxia-inducible factor-1α gene
Chun, Y., Choi, E., Kim, T., Kim, M.-S., & Park, J. (2002) · Biochemical Journal · doi:10.1042/0264-6021:3620071 · Cited by 74 · see citing works
Hypoxia-inducible factor 1 alpha (HIF-1α) gene expression in human ovarian carcinoma
Nakayama, K., Kanzaki, A., Hata, K., Katabuchi, H., Okamura, H., Miyazaki, K., Fukumoto, M., & Takebayashi, Y. (2002) · Cancer Letters · doi:10.1016/s0304-3835(01)00762-5 · Cited by 67 · see citing works
Hypoxia-inducible factor 1α (HIF-1α) correlated with tumor growth and apoptosis in ovarian cancer
Jiang, H., & Feng, Y. (2006) · International Journal of Gynecological Cancer · doi:10.1111/j.1525-1438.2006.00310.x · Cited by 44 · see citing works
Targeting topoisomerase I to inhibit hypoxia inducible factor 1.
Rapisarda, A., Shoemaker, R. H., & Melillo, G. (2004) · PubMed · Cited by 41 · see citing works
Targeting Topoisomerase 1 to inhibit Hypoxia Inducible Factor 1
Rapisarda, A., Shoemaker, R. H., & Melillo, G. (2004) · Cell Cycle · doi:10.4161/cc.3.2.688 · Cited by 41 · see citing works
MgcRacGAP Interacts with HIF-1α and Regulates its Transcriptional Activity
Lyberopoulou, A., Venieris, E., Mylonis, I., Chachami, G., Pappas, I. S., Simos, G., Bonanou, S., & Georgatsou, E. (2007) · Cellular Physiology and Biochemistry · doi:10.1159/000110460 · Cited by 36 · see citing works
Self-citationMitochondria: Oxygen sinks rather than sensors?
Wenger, R. H. (2005) · Medical Hypotheses · doi:10.1016/j.mehy.2005.08.047 · Cited by 36 · see citing works
Nakai, H., Watanabe, Y., Ueda, H., & Hoshiai, H. (2007) · Cancer Letters · doi:10.1016/j.canlet.2006.11.017 · Cited by 22 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Semenza GL Regulation of mammalian O2 homeostasis by hypoxia inducible factor 1 Annu Rev Cell Dev Biol 1999 15 551 78 10611972
- Semenza GL Targeting HIF-1 for cancer therapy Nat Rev Cancer 2003 3 721 32 13130303
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Sorted by citations
Role of hypoxia in cancer therapy by regulating the tumor microenvironment
Jing, X., Yang, F., Shao, C., Wei, K., Xie, M., Shen, H., & Shu, Y. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1089-9 · Cited by 2,054 · see citing works
Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics
Semenza, G. L. (2010) · Oncogene · doi:10.1038/onc.2009.441 · Cited by 1,712 · see citing works
HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression
Keith, B., Johnson, R. S., & Simon, M. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3183 · Cited by 1,693 · see citing works
Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and Treg cells
Facciabene, A., Peng, X., Hagemann, I. S., Balint, K., Barchetti, A., Wang, L.-P., Gimotty, P. A., Gilks, C. B., Lal, P., Zhang, L., et al. (2011) · Nature · doi:10.1038/nature10169 · Cited by 1,376 · see citing works
Oxygen Sensing, Hypoxia-Inducible Factors, and Disease Pathophysiology
Semenza, G. L. (2013) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104720 · Cited by 1,159 · see citing works
Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer
Wigerup, C., Påhlman, S., & Bexell, D. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.04.009 · Cited by 687 · see citing works
“In contrast, many benign tumors show very little or no HIF-1α expression (Zhong et al., 1999; Daponte et al., 2008; Simiantonaki et al., 2008; Mayer et al., 2008b).”
BackgroundDrug repurposing for cancer therapy
Xia, Y., Sun, M., Huang, H., & Jin, W.-L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01808-1 · Cited by 443 · see citing works
“296 Given these insights, targeting the hypoxic TME via drug repurposing may be bene fi cial in the development of oncological agents.”
BackgroundHIF1/2α mediates hypoxia-induced LDHA expression in human pancreatic cancer cells
Cui, X., Han, Z., He, S., Wu, X., Chen, T., Shao, C., Chen, D., Su, N., Chen, Y.-M., Wang, T., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.15266 · Cited by 191 · see citing works
Kolenda, J., Jensen, S. S., Aaberg-Jessen, C., Christensen, K., Andersen, C., Brünner, N., & Kristensen, B. W. (2011) · Journal of Neuro-Oncology · doi:10.1007/s11060-010-0357-8 · Cited by 115 · see citing works
Asare-Werehene, M., Nakka, K. K., Reunov, A., Chiu, C.-T., Lee, W., Abedini, M. R., Wang, P., Shieh, D.-B., Dilworth, F. J., Carmona, E., et al. (2019) · Oncogene · doi:10.1038/s41388-019-1087-9 · Cited by 133 · see citing works
Qin, J., Liu, Y., Lu, Y., Liu, M., Li, M., Li, J., & Wu, L. (2017) · Scientific Reports · doi:10.1038/s41598-017-09244-8 · Cited by 121 · see citing works
Molecular Responses to Hypoxia-Inducible Factor 1α and Beyond
Brocato, J., Chervona, Y., & Costa, M. (2014) · Molecular Pharmacology · doi:10.1124/mol.113.089623 · Cited by 112 · see citing works
Impact of isoflurane on malignant capability of ovarian cancer in vitro
Luo, X., Zhao, H., Hennah, L., Ning, J., Liu, J., Tu, H., & Ma, D. (2014) · British Journal of Anaesthesia · doi:10.1093/bja/aeu408 · Cited by 107 · see citing works
Detection of Hypoxia in Cancer Models: Significance, Challenges, and Advances
Godet, I., Doctorman, S., Wu, F., & Gilkes, D. M. (2022) · Cells · doi:10.3390/cells11040686 · Cited by 105 · see citing works
Pham, E., Birrer, M. J., Eliasof, S. D., Garmey, E. G., Lazarus, D. D., Lee, C. R., Man, S., Matulonis, U. A., Peters, C. G., Xu, P., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2810 · Cited by 94 · see citing works
A therapeutic role for targeting c-Myc/Hif-1- dependent signaling pathways
Podar, K., & Anderson, K. C. (2010) · Cell Cycle · doi:10.4161/cc.9.9.11358 · Cited by 82 · see citing works
The Roles of Exosomal Proteins: Classification, Function, and Applications
Li, X., Yang, L.-X., Wang, C., Li, H., Shi, D., & Wang, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043061 · Cited by 79 · see citing works
Sox9 and Hif-2α regulate TUBB3 gene expression and affect ovarian cancer aggressiveness
Raspaglio, G., Petrillo, M., Martinelli, E., Puma, D. D. L., Mariani, M., Donato, M. D., Filippetti, F., Mozzetti, S., Prislei, S., Zannoni, G. F., et al. (2014) · Gene · doi:10.1016/j.gene.2014.03.037 · Cited by 75 · see citing works
Kim, B., Cho, H., Chung, J., Conway, C. M., Ylaya, K., Kim, J., & Hewitt, S. M. (2013) · Journal of Translational Medicine · doi:10.1186/1479-5876-11-185 · Cited by 74 · see citing works
Cheng, J.-C., Klausen, C., & Leung, P. (2013) · Cancer Letters · doi:10.1016/j.canlet.2012.10.029 · Cited by 73 · see citing works
Histone Deacetylase Inhibitors: The Epigenetic Therapeutics That Repress Hypoxia‐Inducible Factors
Chen, S., & Sang, N. (2010) · BioMed Research International · doi:10.1155/2011/197946 · Cited by 73 · see citing works
IL-6 promotes nuclear translocation of HIF-1α to aggravate chemoresistance of ovarian cancer cells
Xu, S., Yu, C., Ma, X., Li, Y., Shen, Y., Chen, Y., Huang, S., Zhang, T., Deng, W., & Wang, Y. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173817 · Cited by 61 · see citing works
The Role of Dysregulated Glucose Metabolism in Epithelial Ovarian Cancer
Kellenberger, L. D., Bruin, J. E., Greenaway, J. B., Campbell, N., Moorehead, R. A., Holloway, A. C., & Petrik, J. (2010) · Journal of Oncology · doi:10.1155/2010/514310 · Cited by 61 · see citing works
Klemba, A., Bodnar, L., Waś, H., Brodaczewska, K. K., Wcisło, G., Szczylik, C. A., & Kiéda, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249492 · Cited by 59 · see citing works
HIF-1α Is a Rational Target for Future Ovarian Cancer Therapies
Wang, X., Du, Z., Xu, T., Wang, X., Li, W., Gao, J., Li, J., & Zhu, H. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.785111 · Cited by 46 · see citing works
Gomez-Roman, N., Sahasrabudhe, N. M., McGregor, F., Chalmers, A. J., Cassidy, J., & Plumb, J. A. (2016) · Oncotarget · doi:10.18632/oncotarget.7998 · Cited by 43 · see citing works
Loss of DOK2 induces carboplatin resistance in ovarian cancer via suppression of apoptosis
Lum, E., Vigliotti, M., Banerjee, N., Cutter, N. L., Wrzeszczyński, K. O., Khan, S. A., Kamalakaran, S., Levine, D. A., Dimitrova, N., & Lucito, R. (2013) · Gynecologic Oncology · doi:10.1016/j.ygyno.2013.05.002 · Cited by 45 · see citing works
Naruse, T., Kawasaki, G., Yanamoto, S., Mizuno, A., & Umeda, M. (2011) · PubMed · Cited by 40 · see citing works
Metabolic factors contribute to T‐cell inhibition in the ovarian cancer ascites
Gong, Y., Yang, J., Wang, Y., Xue, L., & Wang, J. (2020) · International Journal of Cancer · doi:10.1002/ijc.32990 · Cited by 39 · see citing works
A computational framework for complex disease stratification from multiple large-scale datasets
Meulder, B. D., Lefaudeux, D., Bansal, A. T., Mazein, A., Chaiboonchoe, A., Ahmed, H., Balaur, I., Saqi, M. A. S., Pellet, J., Ballereau, S. J., et al. (2018) · BMC Systems Biology · doi:10.1186/s12918-018-0556-z · Cited by 37 · see citing works
Braicu, E. I., Luketina, H., Richter, R., Castillo‐Tong, D. C., Lambrechts, S., Mahner, S., Concin, N., Mentze, M., Zeillinger, R., Vergote, I. B., et al. (2014) · OncoTargets and Therapy · doi:10.2147/ott.s65373 · Cited by 34 · see citing works
A four-hypoxia-genes-based prognostic signature for oral squamous cell carcinoma
Zhao, C., Zhou, Y., Ma, H., Wang, J., Guo, H., & Liu, H. (2021) · BMC Oral Health · doi:10.1186/s12903-021-01587-z · Cited by 31 · see citing works
Townsend, K. N., Spowart, J. E., Huwait, H., Eshragh, S., West, N. R., Elrick, M. A., Kalloger, S. E., Anglesio, M., Watson, P. H., Huntsman, D. G., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082406 · Cited by 29 · see citing works
Jin, Y., Wang, H., Liang, X., Ma, J., & Wang, Y. (2014) · Tumor Biology · doi:10.1007/s13277-014-2059-x · Cited by 27 · see citing works
PFKFB4 interacts with FBXO28 to promote HIF-1α signaling in glioblastoma
Phillips, E. S., Balß, J., Bethke, F., Pusch, S., Christen, S., Hielscher, T., Schnölzer, M., Fletcher, M. N. C., Habel, A., Tessmer, C., et al. (2022) · Oncogenesis · doi:10.1038/s41389-022-00433-3 · Cited by 26 · see citing works
Li, M., Li, L., Cheng, X., Li, L., & Tu, K. (2023) · Experimental Cell Research · doi:10.1016/j.yexcr.2023.113851 · Cited by 26 · see citing works
Kyykallio, H., Oikari, S., Álvez, M. B., Gallardo-Dodd, C. J., Capra, J., & Rilla, K. J. (2020) · Cancers · doi:10.3390/cancers12071908 · Cited by 24 · see citing works
Yu, X., Wang, Y., Qiu, H., Song, H., Feng, D., Jiang, Y. Z., Deng, S., Meng, H., & Geng, J. (2018) · BioMed Research International · doi:10.1155/2018/3145689 · Cited by 22 · see citing works
Han, Y., Wang, X., Xia, K., & Su, T. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-4990 · Cited by 20 · see citing works
Pereira, M., Matuszewska, K., Jamieson, C., & Petrik, J. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.772349 · Cited by 21 · see citing works
Lipocalin2 as a plasma marker for tumors with hypoxic regions
Nakamura, I., Hama, S., Itakura, S., Takasaki, I., Nishi, T., Tabuchi, Y., & Kogure, K. (2014) · Scientific Reports · doi:10.1038/srep07235 · Cited by 20 · see citing works
Duan, L., Tao, J., Yang, X., Ye, L., Wu, Y., He, Q., Duan, Y., Chen, L., & Zhu, J. (2020) · Journal of Ovarian Research · doi:10.1186/s13048-020-00646-3 · Cited by 19 · see citing works
Nanotechnology in Advancing Chimeric Antigen Receptor T Cell Therapy for Cancer Treatment
Kang, X., Mita, N., Zhou, L., Wu, S., Yue, Z., Babu, R. J., & Chen, P. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16091228 · Cited by 19 · see citing works
Lindgren, A., Anttila, M., Rautiainen, S., Arponen, O., Hämäläinen, K. M., Könönen, M., Vanninen, R., & Sallinen, H. (2019) · PLoS ONE · doi:10.1371/journal.pone.0221340 · Cited by 18 · see citing works
Jin, Y., Wang, H., Ma, X., Liang, X., Liu, X., & Wang, Y. (2015) · PLoS ONE · doi:10.1371/journal.pone.0127229 · Cited by 17 · see citing works
Hypoxia A Typical Target in Human Lung Cancer Therapy
Ullah, A., Shehzadi, S., Ullah, N., Nawaz, T., Iqbal, H., & Aziz, T. (2023) · Current Protein and Peptide Science · doi:10.2174/0113892037252820231114045234 · Cited by 17 · see citing works
Tissue Factor–Factor VII Complex as a Key Regulator of Ovarian Cancer Phenotypes
Koizume, S., & Miyagi, Y. (2015) · Biomarkers in Cancer · doi:10.4137/bic.s29318 · Cited by 17 · see citing works
Twist2 promotes ovarian cancer cell survival through activation of Akt
Mao, Y., Xu, J., Song, G., Zhang, N., & YIN, H. (2013) · Oncology Letters · doi:10.3892/ol.2013.1316 · Cited by 13 · see citing works
MADEJ, J. A., Madej, J. P., Dzięgiel, P., Puła, B., & Nowak, M. (2013) · Acta veterinaria Scandinavica · doi:10.1186/1751-0147-55-73 · Cited by 13 · see citing works
Wang, Y., Li, B. X., & Li, X. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.783666 · Cited by 11 · see citing works
SNAIL gene inhibited by hypoxia-inducible factor 1α (HIF-1α) in epithelial ovarian cancer
Zhang, P., Liu, Y., Feng, Y., & Gao, S. (2016) · International Journal of Immunopathology and Pharmacology · doi:10.1177/0394632016641423 · Cited by 11 · see citing works
Ni, J., & Anping, N. (2021) · PLoS ONE · doi:10.1371/journal.pone.0248019 · Cited by 11 · see citing works
Hypoxia-inducible factor-1α as prognostic marker
Lassoued, A. B., Beaufils, N., Dalès, J.-P., & Gabert, J. A. (2012) · Expert Opinion on Medical Diagnostics · doi:10.1517/17530059.2012.719022 · Cited by 10 · see citing works
Dai, D., Li, C., Xia, H., Qi, C., Lyu, M., Yao, Z., Zhang, F., Zhu, Y., Qi, M., & Cao, X. (2024) · Gynecologic Oncology · doi:10.1016/j.ygyno.2024.07.688 · Cited by 9 · see citing works
Development of small molecule inhibitors of hypoxia-inducible factors for cancer therapy
Semenza, G. L. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100075 · Cited by 10 · see citing works
In search of new prognostic molecular markers in ovarian cancer
Laatio, L. (2012) · Cited by 7 · see citing works
Roy, S., Das, A., Vernekar, M., Mandal, S., & Chatterjee, N. (2022) · BioMed Research International · doi:10.1155/2022/5346091 · Cited by 8 · see citing works
Makaritsis, K. P., Kotidis, C., Papacharalampous, K., Kouvaras, E., Poulakida, E., Tarantilis, P. Α., Asprodini, E., Ntaios, G., Koukoulis, G. Κ., Dalekos, G. Ν., et al. (2022) · Coronary Artery Disease · doi:10.1097/mca.0000000000001142 · Cited by 7 · see citing works
Self-citationGünaydın, B., Yiğittürk, G., & Elbe, H. (2023) · Romanian Journal of Morphology and Embryology · doi:10.47162/rjme.64.3.07 · Cited by 7 · see citing works
Al‐Sharaky, D. R. (2016) · JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · doi:10.7860/jcdr/2016/19576.7805 · Cited by 7 · see citing works
HIF-1 inactivation empowers HIF-2 to drive hypoxia adaptation in aggressive forms of medulloblastoma
Contenti, J., Guo, Y., Larcher, M., Mirabal-Ortega, L., Rouleau, M., Irondelle, M., Tiroille, V., Mazzu, A., Duranton-Tanneur, V., Pedeutour, F., et al. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02100-5 · Cited by 6 · see citing works
Circulating levels of hydroxylated bradykinin function as an indicator of tissue HIF-1α expression
Liu, Y., Gu, Y., Ng, S., Deng, Z., Lyon, C. J., Koay, E. J., Ning, B., Katz, M. H. G., Chiao, P. J., Fan, J., et al. (2020) · 中国科学通报：英文版 · doi:10.1016/j.scib.2020.04.023 · Cited by 4 · see citing works
Wu, T., Yao, Y., Sun, R., Wang, H., Zhang, J., Yin, X., Zhou, Q., & Huangfu, C. (2021) · Science Progress · doi:10.1177/00368504211026417 · Cited by 4 · see citing works
Wilczyński, J. R., Wilczyński, M., & Paradowska, E. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1201497 · Cited by 4 · see citing works
Britten, J., Malik, M., Pekny, C. J., DeAngelis, A., & Catherino, W. H. (2020) · F&S Science · doi:10.1016/j.xfss.2020.09.003 · Cited by 3 · see citing works
Prognostic Value of UBE2S, HIF‐1α, and FOXM1 Expression in Esophageal Squamous Cell Carcinoma
Li, W., Zhou, K., Li, M., Su, L., Liu, X., Lv, Y., & Ma, Y. (2025) · Analytical Cellular Pathology · doi:10.1155/ancp/3557238 · Cited by 2 · see citing works
Polajžer, S., Lukanović, D., Škof, E., Kobal, B., & Černe, K. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1757708 · Cited by 2 · see citing works
Non-canonical approaches to targeting hypoxic tumors.
Zhao, S., & El‐Deiry, W. S. (2022) · PubMed Central · Cited by 1 · see citing works
Zhang, W., Lin, Y., Jiang, J., & Hu, Y. (2024) · Current Problems in Cancer · doi:10.1016/j.currproblcancer.2024.101155 · Cited by 1 · see citing works
Tissue Expression of Hypoxia-Inducible Factor 1 Alpha (HIF-1A) in Wilms Tumor
Tekin, E., Dınız, G., Yıldırım, H. T., Öniz, H., & Vergin, C. R. (2019) · Journal of Dr Behcet Uz Children s Hospital · doi:10.5222/buchd.2018.53386 · Cited by 1 · see citing works
Patient-specific tumor biology-based selection of ovarian cancer therapy
Fruehauf, J. P. (2010) · Therapy · doi:10.2217/thy.10.20 · Cited by 1 · see citing works
Understanding CD8 T cell function under the tumour environment condition hypoxia
Townsend, K. N. (2012) · UVic’s Research and Learning Repository (University of Victoria)
Alternative treatment of chemoresistant, recurrent or advanced ovarian cancer. Part I
Wilczyński, J. R. (2011) · DOAJ (DOAJ: Directory of Open Access Journals)
HIF1α and SOX2 expression in cervical squamous cell carcinoma
Milenković, S. J., Terzić, T., Vranes, B., & Soldatović, I. (2018) · Vojnosanitetski pregled · doi:10.2298/vsp171213043m
El-Kady, N., Mohamed, A. E.-N. S., Aiad, H. A. S., El‐Wahed, M. M. A., Asaad, N. Y., & Allam, D. M. (2018) · Egyptian Journal of Pathology · doi:10.1097/01.xej.0000542233.99011.a6
Perdikouri, Ε.-I., Liaskos, C., Papacharalampous, K., Nasi, D., Kostopoulou, E., Koukoulis, G. Κ., & Papandreou, C. N. (2019) · Journal of Molecular Biomarkers & Diagnosis
Self-citationAssociation Hypoxia Inducible Factors-1 Alpha (HIF-1 α) Levels and Epithelial Ovarian Cancer (EOC)
Asis, A., Pelupessy, N. U., Mailoa, J., & Chalid, M. T. (2023) · Indonesian Journal of Obstetrics & Gynecology Science · doi:10.24198/obgynia.v6i1.438
Molecular mechanisms of glucose metabolism disorders in tumors of the female reproductive system
Kovaleva, E. Y., Kantimirova, R. R., Gunina, T. K., Vlasenko, E. V., Salychin, D. O., Khulagova, D. S., Kochkin, A., Mamatkova, V. A., Zhakov, N. S., Bezmaternykh, G. K., et al. (2025) · Obstetrics Gynecology and Reproduction · doi:10.17749/2313-7347/ob.gyn.rep.2025.650
Duan, L., Tao, J., Yang, X., Ye, L., Wu, Y., He, Q., Duan, Y., Chen, L., & Zhu, J. (2020) · Figshare · doi:10.6084/m9.figshare.12160116
Kumar, A. S., Kumar, M., Rai, S., Sonker, P., & Kumar, A. (2026) · Cytotechnology · doi:10.1007/s10616-026-01034-3
- Authors
- Daponte, A., Ioannou, M., Mylonis, I., Simos, G., Minas, M., Messinis, I. E., & Koukoulis, G.
- Affiliations
- University of Thessaly (GR)
- Corresponding author
- Daponte, Alexandros
- Venue
- BMC Cancer
- Published
- 2008-11-16
- Volume
- 8
- Issue
- 1
- Pages
- 335-335
- ISSN
- 1471-2407 (ISSN-L)
- PMC
- PMC2651893
- OpenAlex
- W2114133947
- Cited by
- 82
- References
- 34
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 7 · 2013: 6 · 2012: 4
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Cancer (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- University of Thessaly Institutional Repository (University of Thessaly) (submittedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Keywords
- HIF-1α, HIF-1, serous ovarian cancer, prognostic factors, overall survival, progression-free interval, paclitaxel, carboplatin, tumor hypoxia, tumor angiogenesis, TNF-α, tumor cell proliferation
- MeSH terms
- Female, Humans, Immunohistochemistry, Neoplasm Staging, Ovarian Neoplasms, Prognosis, Survival, Gene Expression, Hypoxia-Inducible Factor 1, alpha Subunit
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