Transplacental Carcinogenesis by Stilbestrol
Abstract
Herbst, Ulfelder and Poskanzer1 were the first to notice a high correlation between adenocarcinoma of the vagina in adolescent girls and prior maternal ingestion of diethylstilbestrol. This is a stunning observation. It is supported by five more cases described in this issue by Greenwald et al. In a previous editorial2 Langmuir discussed some clinical and scientific implications of this discovery. Further speculations are now warranted.Neither Herbst nor Greenwald studied a large number of mothers with repeated bleeding or previous pregnancy loss who did not receive stilbestrol. This omission is irrelevant, however, because of the extreme rarity of adenocarcinoma of . . .
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 ability of tumor cells to induce new blood vessel formation is essential for tumor growth and metastatic cancer dissemination.
“The ability of tumor cells to induce new blood vessel formation is essential for tumor growth and metastatic cancer dissemination44,263.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [44]
Cites
Herbst, A. L., Ulfelder, H., & Poskanzer, D. C. (1971) · New England Journal of Medicine · doi:10.1056/nejm197104222841604 · Cited by 2,545 · see citing works
Herbst, A. L., & Scully, R. E. (1970) · Cancer · doi:10.1002/1097-0142(197004)25:4 · Cited by 458 · see citing works
New Environmental Factor in Congenital Disease
Langmuir, A. D. (1971) · New England Journal of Medicine · doi:10.1056/nejm197104222841611 · Cited by 19 · see citing works
Meissner (1957) · doi:10.1002/1097-0142(195705/06)10:3
Flagged first, then by citations
Cited by
Sorted by citations
Microenvironmental regulation of tumor progression and metastasis
Quail, D. F., & Joyce, J. A. (2013) · Nature Medicine · doi:10.1038/nm.3394 · Cited by 7,994 · see citing works
Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy
Jain, R. K. (2005) · Science · doi:10.1126/science.1104819 · Cited by 5,527 · see citing works
Endostatin: an endogenous inhibitor of angiogenesis and tumor growth
O'Reilly, M. S., Boehm, T., Shing, Y., Fukai, N., Vasios, G., Lane, W. S., Flynn, E., Birkhead, J. R., Olsen, B. R., & Folkman, J. (1997) · Cell · doi:10.1016/s0092-8674(00)81848-6 · Cited by 4,486 · see citing works
Self-citationVascular-specific growth factors and blood vessel formation
Yancopoulos, G. D., Davis, S., Gale, N. W., Rudge, J. S., Wiegand, S. J., & Holash, J. (2000) · Nature · doi:10.1038/35025215 · Cited by 3,699 · see citing works
Factors affecting the clearance and biodistribution of polymeric nanoparticles
Alexis, F., Pridgen, E., Molnar, L. K., & Farokhzad, O. C. (2008) · Molecular Pharmaceutics · doi:10.1021/mp800051m · Cited by 3,699 · see citing works
Functional Polarization of Tumour-Associated Macrophages by Tumour-Derived Lactic Acid
Colegio, O. R., Chu, N.-Q., Szabo, A. L., Chu, T., Rhebergen, A. M., Jairam, V., Cyrus, N., Brokowski, C. E., Eisenbarth, S. C., Phillips, G. M., et al. (2014) · Nature · doi:10.1038/nature13490 · Cited by 3,046 · see citing works
Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis
Bergers, G., Brekken, R., McMahon, G., Vu, T. H., Itoh, T., Tamaki, K., Tanzawa, K., Thorpe, P., Itohara, S., Werb, Z., et al. (2000) · Nature Cell Biology · doi:10.1038/35036374 · Cited by 2,797 · see citing works
Angiogenesis as a therapeutic target
Ferrara, N., & Kerbel, R. S. (2005) · Nature · doi:10.1038/nature04483 · Cited by 2,653 · see citing works
Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer
Ferrara, N., Hillan, K. J., Gerber, H.-P., & Novotny, W. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1381 · Cited by 2,625 · see citing works
Pegaptanib for neovascular age-related macular degeneration
Gragoudas, E. S., Adamis, A. P., Cunningham, E. T., Feinsod, M., & Guyer, D. R. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa042760 · Cited by 2,337 · see citing works
Induction of angiogenesis during the transition from hyperplasia to neoplasia
Folkman, J., Watson, K., Ingber, D., & Hanahan, D. (1989) · Nature · doi:10.1038/339058a0 · Cited by 1,879 · see citing works
Self-citationComprehensive review of targeted therapy for colorectal cancer
Xie, Y.-H., Chen, Y.-X., & Fang, J.-Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0116-z · Cited by 1,687 · see citing works
The discovery of receptor tyrosine kinases: targets for cancer therapy
Gschwind, A., Fischer, O. M., & Ullrich, A. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1360 · Cited by 1,227 · see citing works
Folkman, J. (2006) · Annual Review of Medicine · doi:10.1146/annurev.med.57.121304.131306 · Cited by 1,209 · see citing works
Self-citationCycling hypoxia and free radicals regulate angiogenesis and radiotherapy response
Dewhirst, M. W., Cao, Y., & Moeller, B. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2397 · Cited by 1,022 · see citing works
Clinical applications of angiogenic growth factors and their inhibitors
Ferrara, N., & Alitalo, K. (1999) · Nature Medicine · doi:10.1038/70928 · Cited by 1,004 · see citing works
Pancreatic cancer stroma: an update on therapeutic targeting strategies
Hosein, A. N., Brekken, R. A., & Maitra, A. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0300-1 · Cited by 950 · see citing works
TGFβ biology in cancer progression and immunotherapy
Derynck, R., Turley, S. J., & Akhurst, R. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0403-1 · Cited by 944 · see citing works
Enhanced Permeability and Retention (EPR) Effect for Anticancer Nanomedicine Drug Targeting
Greish, K. (2010) · Methods in Molecular Biology · doi:10.1007/978-1-60761-609-2_3 · Cited by 841 · see citing works
Transport of drugs from blood vessels to tumour tissue
Dewhirst, M. W., & Secomb, T. W. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.93 · Cited by 749 · see citing works
Antiangiogenic therapy: impact on invasion, disease progression, and metastasis
Ebos, J. M. L., & Kerbel, R. S. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.21 · Cited by 685 · see citing works
Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia
Conley, S. J., Gheordunescu, E., Kakarala, P., Newman, B., Korkaya, H., Heath, A. N., Clouthier, S. G., & Wicha, M. S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018866109 · Cited by 663 · see citing works
Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1α
Soeda, A., Park, M., Lee, D., Mintz, A., Androutsellis-Theotokis, A., McKay, R. D., Engh, J., Iwama, T., Kunisada, T., Kassam, A. B., et al. (2009) · Oncogene · doi:10.1038/onc.2009.252 · Cited by 656 · see citing works
Why are tumour blood vessels abnormal and why is it important to know?
Nagy, J. A., Chang, S.-H., Dvorak, A. M., & Dvorak, H. F. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6604929 · Cited by 611 · see citing works
Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment
Yi, M., Jiao, D., Qin, S., Chu, Q., Wu, K., & Li, A. (2019) · Molecular Cancer · doi:10.1186/s12943-019-0974-6 · Cited by 608 · see citing works
Biomarkers of response and resistance to antiangiogenic therapy
Jain, R. K., Duda, D. G., Willett, C. G., Sahani, D. V., Zhu, A. X., Loeffler, J. S., Batchelor, T. T., & Sorensen, A. G. (2009) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2009.63 · Cited by 572 · see citing works
A history of exploring cancer in context
Maman, S., & Witz, I. P. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0006-7 · Cited by 502 · see citing works
The discovery of first-in-class drugs: origins and evolution
Eder, J., Sedrani, R., & Wiesmann, C. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4336 · Cited by 514 · see citing works
The parallel lives of angiogenesis and immunosuppression: cancer and other tales
Motz, G. T., & Coukos, G. (2011) · Nature Reviews Immunology · doi:10.1038/nri3064 · Cited by 481 · see citing works
Maeda, H., & Khatami, M. (2018) · Clinical and Translational Medicine · doi:10.1186/s40169-018-0185-6 · Cited by 491 · see citing works
Kloepper, J., Riedemann, L., Amoozgar, Z., Seano, G., Susek, K., Yu, V., Dalvie, N., Amelung, R. L., Datta, M., Song, J. W., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525360113 · Cited by 357 · see citing works
A three-dimensional in vitro model of tumor cell intravasation
Ehsan, S. M., Welch-Reardon, K. M., Waterman, M. L., Hughes, C. C. W., & George, S. C. (2014) · Integrative Biology · doi:10.1039/c3ib40170g · Cited by 196 · see citing works
Endothelial Cells in the Tumor Microenvironment
Sobierajska, K., Ciszewski, W. M., Sacewicz-Hofman, I., & Niewiarowska, J. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-37184-5_6 · Cited by 179 · see citing works
Targeting vascular and leukocyte communication in angiogenesis, inflammation and fibrosis
Kreuger, J., & Phillipson, M. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.2 · Cited by 160 · see citing works
The Fluid Mechanics of Cancer and Its Therapy
Koumoutsakos, P., Pivkin, I., & Milde, F. (2013) · Annual Review of Fluid Mechanics · doi:10.1146/annurev-fluid-120710-101102 · Cited by 129 · see citing works
Biomimetic Model of Tumor Microenvironment on Microfluidic Platform
Chung, M., Ahn, J., Son, K., Kim, S., & Jeon, N. L. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700196 · Cited by 126 · see citing works
Policastro, L. L., Ibañez, I. L., Notcovich, C., Duran, H. A., & Podhajcer, O. L. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4367 · Cited by 120 · see citing works
Jain, R. K., Finn, A. V., Kolodgie, F. D., Gold, H. K., & Virmani, R. (2007) · Nature Clinical Practice Cardiovascular Medicine · doi:10.1038/ncpcardio0979 · Cited by 117 · see citing works
Local iron homeostasis in the breast ductal carcinoma microenvironment
Marques, O., Porto, G., Rêma, A., Faria, F., Cruz Paula, A., Gomez-Lazaro, M., Silva, P., Martins da Silva, B., & Lopes, C. (2016) · BMC Cancer · doi:10.1186/s12885-016-2228-y · Cited by 90 · see citing works
Zhou, J. X., Taramelli, R., Pedrini, E., Knijnenburg, T., & Huang, S. (2017) · Scientific Reports · doi:10.1038/s41598-017-09307-w · Cited by 85 · see citing works
Sun, B., Zhang, S., Ni, C., Zhang, D., Liu, Y., Zhang, W., Zhao, X., Zhao, C., & Shi, M. (2005) · Stem Cells and Development · doi:10.1089/scd.2005.14.292 · Cited by 72 · see citing works
Molecular heterogeneity of tumor endothelium
Aird, W. C. (2009) · Cell and Tissue Research · doi:10.1007/s00441-008-0672-y · Cited by 66 · see citing works
Gestational sac diameter in very early pregnancy as a predictor of fetal outcome
Oh, J. S., Wright, G., & Coulam, C. B. (2002) · Ultrasound in Obstetrics & Gynecology · doi:10.1046/j.1469-0705.2002.00774.x · Cited by 64 · see citing works
Activated hepatic stellate cells promote angiogenesis via interleukin-8 in hepatocellular carcinoma
Zhu, B., Lin, N., Zhang, M., Zhu, Y., Cheng, H., Chen, S., Ling, Y., Pan, W., & Xu, R. (2015) · Journal of Translational Medicine · doi:10.1186/s12967-015-0730-7 · Cited by 58 · see citing works
Casillas, A. L., Chauhan, S. S., Toth, R. K., Sainz, A. G., Clements, A. N., Jensen, C. C., Langlais, P. R., Miranti, C. K., Cress, A. E., & Warfel, N. A. (2021) · Oncogene · doi:10.1038/s41388-021-01915-1 · Cited by 44 · see citing works
Aflibercept in the Treatment of Metastatic Colorectal Cancer
Wang, T.-F., & Lockhart, A. C. (2012) · Clinical Medicine Insights: Oncology · doi:10.4137/cmo.s7432 · Cited by 44 · see citing works
Recent concepts of antiangiogenic therapy
Konno, H., Yamamoto, M., & Ohta, M. (2010) · Surgery Today · doi:10.1007/s00595-009-4150-2 · Cited by 16 · see citing works
The history of angiogenesis inhibitors
Ribatti, D. (2007) · Leukemia · doi:10.1038/sj.leu.2404756 · Cited by 15 · see citing works
- Authors
- Folkman, J.
- Corresponding author
- Folkman, Judah
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1971-08-12
- Volume
- 285
- Issue
- 7
- Pages
- 404-405
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2054728198
- Cited by
- 2,640
- References
- 4
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 13 · 2023: 12 · 2022: 19 · 2021: 46 · 2020: 44 · 2019: 57 · 2018: 61 · 2017: 79 · 2016: 88 · 2015: 113 · 2014: 105 · 2013: 139 · 2012: 152
- FWCI
- 14.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- diethylstilbestrol, transplacental carcinogenesis, vaginal adenocarcinoma, adolescent girls, maternal exposure, miscarriage, endometrial cancer
- MeSH terms
- Adenocarcinoma, Age Factors, Carcinogens, Diethylstilbestrol, Female, Humans, Maternal-Fetal Exchange, Pregnancy, Pregnancy Complications, Vaginal Neoplasms
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