Enhancement of Regression of Cervical Intraepithelial Neoplasia II (Moderate Dysplasia) With Topically Applied All- trans -Retinoic Acid: a Randomized Trial
Open accessAbstract
BACKGROUND: Retinoids enhance differentiation of most epithelial tissues. Epidemiologic studies have shown an inverse relationship between dietary intake or serum levels of vitamin A and the development of cervical dysplasia and/or cervical cancer. Pilot and phase I investigations demonstrated the feasibility of the local delivery of all-trans-retinoic acid (RA) to the cervix using a collagen sponge insert and cervical cap. A phase II trial produced a clinical complete response rate of 50%. PURPOSE: This randomized phase III trial was designed to determine whether topically applied RA reversed moderate cervical intraepithelial neoplasia (CIN) II or severe CIN. METHODS: Analyses were based on 301 women with CIN (moderate dysplasia, 151 women; severe dysplasia, 150 women), evaluated by serial colposcopy, Papanicolaou cytology, and cervical biopsy. Cervical caps with sponges containing either 1.0 mL of 0.372% beta-trans-RA or a placebo were inserted daily for 4 days when women entered the trial, and for 2 days at months 3 and 6. Patients receiving treatment and those receiving placebo were similar with respect to age, ethnicity, birth-control methods, histologic features of the endocervical biopsy specimen and koilocytotic atypia, and percentage of involvement of the cervix at study. Treatment effects were compared using Fisher's exact test and logistic regression methods. Side effects were recorded, and differences were compared using Fisher's exact test. RESULTS: RA increased the complete histologic regression rate of CIN II from 27% in the placebo group to 43% in the retinoic acid treatment group (P = .041). No treatment difference between the two arms was evident in the severe dysplasia group. More vaginal and vulvar side effects were seen in the patients receiving RA, but these effects were mild and reversible. CONCLUSIONS: A short course of locally applied RA can reverse CIN II, but not more advanced dysplasia, with acceptable local side effects. IMPLICATIONS: A derivative of vitamin A can reverse or suppress an epithelial preneoplasia, lending further support to the notion that chemoprevention of human cancer is feasible.
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 formulation did not reach the market, likely because it was not sufficient to reverse or suppress more advanced dysplasia with acceptable local side effects in phase III clinical trial.
“the formulation did not reach the market, likely because it was not sufficient to reverse or suppress more advanced dysplasia with acceptable local side effects in phase III clinical trial107.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [107]
Cites
A human retinoic acid receptor which belongs to the family of nuclear receptors
Petkovich, M., Brand, N. J., Krust, A., & Chambon, P. (1987) · Nature · doi:10.1038/330444a0 · Cited by 2,214 · see citing works
Hong, W. K., Lippman, S. M., Itri, L. M., Karp, D. D., Lee, J. S., Byers, R. M., Schantz, S. P., Kramer, A., Lotan, R., Peters, L. J., et al. (1990) · New England Journal of Medicine · doi:10.1056/nejm199009203231205 · Cited by 1,365 · see citing works
Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells
Lotan, R. (1980) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/0304-419x(80)90021-9 · Cited by 1,072 · see citing works
13-cis-Retinoic Acid in the Treatment of Oral Leukoplakia
Hong, W. K., Endicott, J., Itri, L. M., Doos, W. G., Batsakis, J. G., Bell, R. H., Fofonoff, S. A., Byers, R., Atkinson, E. N., Vaughan, C. W., et al. (1986) · New England Journal of Medicine · doi:10.1056/nejm198612113152401 · Cited by 811 · see citing works
Histological Typing of Female Genital Tract Tumours
Scully, R., Bonfiglio, T., Kurman, R., et al. (1994) · World Health Organization International Histological Classification of Tumours · doi:10.1007/978-3-642-85014-1 · Cited by 433
Adjuvant treatment of stage I lung cancer with high-dose vitamin A.
Pastorino, U., Infante, M. V., Maioli, M., Chiesa, G., Buyse, M. E., Firket, P., Rosmentz, N., Clerici, M., Soresi, E., & Valente, M. (1993) · Journal of Clinical Oncology · doi:10.1200/jco.1993.11.7.1216 · Cited by 350 · see citing works
Chiesa, F., Tradati, N., Marazza, M., et al. (1992) · European Journal of Cancer Part B Oral Oncology · doi:10.1016/0964-1955(92)90035-y · Cited by 111
Singh, V. N., & Gaby, S. (1991) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/53.1.386s · Cited by 68 · see citing works
Surwit, E. A., Graham, V., Droegemueller, W., et al. (1982) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(82)90016-3 · Cited by 62
Self-citationDorr, R., Surwit, E. A., Droegemueller, W., et al. (1982) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820160609 · Cited by 25
Self-citation
Flagged first, then by citations
10 of the 20 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Hussain, S. P., Hofseth, L. J., & Harris, C. C. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1046 · Cited by 1,690 · see citing works
Polyamines and cancer: old molecules, new understanding
Gerner, E. W., & Meyskens, F. L. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1454 · Cited by 1,163 · see citing works
Self-citationRecent Advances in Chemoprevention of Cancer
Hong, W. K., & Sporn, M. B. (1997) · Science · doi:10.1126/science.278.5340.1073 · Cited by 826 · see citing works
The promise of retinoids to fight against cancer
Altucci, L., & Gronemeyer, H. (2001) · Nature Reviews Cancer · doi:10.1038/35106036 · Cited by 773 · see citing works
Lotan, R., Xu, X., Lippman, S. M., Ro, J. Y., Lee, J. S., Lee, J. J., & Hong, W. K. (1995) · New England Journal of Medicine · doi:10.1056/nejm199505253322103 · Cited by 405 · see citing works
Tainio, K., Athanasiou, A., Tikkinen, K. A. O., Aaltonen, R. L., Cárdenas, J. L., Hernándes, Livson, S., Jakobsson, M., Joronen, K. M., Kiviharju, M., et al. (2018) · BMJ · doi:10.1136/bmj.k499 · Cited by 405 · see citing works
Evidence for Frequent Regression of Cervical Intraepithelial Neoplasia–Grade 2
Castle, P. E., SCHIFFMAN, M. H., Wheeler, C. M., & Solomon, D. (2009) · Obstetrics and Gynecology · doi:10.1097/aog.0b013e31818f5008 · Cited by 383 · see citing works
O’Shaughnessy, J., Kelloff, G. J., Gordon, G., Dannenberg, A. J., Hong, W. K., Fabian, C. J., Sigman, C. C., Bertagnolli, M. M., Stratton, S. P., Lam, S. C., et al. (2002) · PubMed · Cited by 381 · see citing works
Self-citationDevelopment of difluoromethylornithine (DFMO) as a chemoprevention agent.
Meyskens, F. L., & Gerner, E. W. (1999) · PubMed · Cited by 337 · see citing works
Self-citationTsao, A. S., Kim, E. S., & Hong, W. K. (2004) · CA A Cancer Journal for Clinicians · doi:10.3322/canjclin.54.3.150 · Cited by 334 · see citing works
“041) in the moderate dysplasia group but had no effect in severe dysplasia.(287) Indole-3-carbinol (I-3-C), a DNA adduct reducer, has been studied in 30 patients with CIN 2 or 3.”
BackgroundInfluentialRetinoids and their receptors in cancer development and chemoprevention
Sun, S., & Lotan, R. (2002) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(01)00144-5 · Cited by 324 · see citing works
“had no effect on more severe dysplasia [96].”
BackgroundLippman, S. M., Lee, J. J., Karp, D. D., Vokes, E. E., Benner, S. E., Goodman, G. E., Khuri, F. R., Marks, R. S., Winn, R., Fry, W. A., et al. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.8.605 · Cited by 321 · see citing works
Placebo-Controlled Trial of Indole-3-Carbinol in the Treatment of CIN
Bell, M. C., Crowley-Nowick, P., Bradlow, H. L., et al. (2000) · Gynecologic Oncology · doi:10.1006/gyno.2000.5847 · Cited by 265 · see citing works
“Chemoprevention is the attempt to use natural and synthetic compounds to intervene in the early precancerous stages of carcinogenesis, before invasive disease begins [1–4].”
BackgroundAntioxidants in cancer therapy; their actions and interactions with oncologic therapies.
Lamson, D. W., & Brignall, M. S. (1999) · PubMed · Cited by 241 · see citing works
Trimble, C. L., Piantadosi, S., Gravitt, P., Ronnett, B., Pizer, E., Elko, A., Wilgus, B., Yutzy, W., Daniel, R., Shah, K., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-2599 · Cited by 234 · see citing works
Epigenetics of cervical cancer. An overview and therapeutic perspectives
Dueñas‐González, A., Lizano, M., Candelaria, M., Cetina, L., Arce, C., & Cervera, E. (2005) · Molecular Cancer · doi:10.1186/1476-4598-4-38 · Cited by 231 · see citing works
“In cervical cancer, the RARβ2 gene is of particular interest because retinoic acid inhibits transformation of human keratinocytes by HPV-16 [196] and leads to regression of moderate cervical dysplasia [197].”
BackgroundRetinoids: present role and future potential
Evans, T. R. J., & Kaye, S. B. (1999) · British Journal of Cancer · doi:10.1038/sj.bjc.6690312 · Cited by 218 · see citing works
Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions
Ahn, W.-S., Yoo, J. J., Huh, S.-W., et al. (2003) · European Journal of Cancer Prevention · doi:10.1097/00008469-200310000-00007 · Cited by 212 · see citing works
“In other clinical studies, retinamide II shows positive effects on removal of cervical lesions by 68.7% while all-trans-retinoic acid and indole3-carbinol in the form of a cervical cap have also been demonstrated to be effective (Meyskens and Surwit, 1985; Meyskens et al., 1994; Bell et al., 2000).”
BackgroundInfluentialRudzińska, A., Juchaniuk, P., Oberda, J., Wiśniewska, J., Wojdan, W., Szklener, K., & Mańdziuk, S. (2023) · Nutrients · doi:10.3390/nu15081896 · Cited by 223 · see citing works
Castle, P. E., Stoler, M. H., Solomon, D., et al. (2007) · American Journal of Clinical Pathology · doi:10.1309/pt3pnc1ql2f4d2vl · Cited by 202 · see citing works
“of cases (%) 53 (10) 31 (6) 54 (10) 8 (1) 146 (27) Carc HPV+ (%) 96 94 96 75 95 HPV-16+ (%) 58 53 59 63 58 Missing No.”
Moon, T. E., Levine, N. S., Cartmel, B., Bangert, J. L., Rodney, S., Dong, Q., Peng, Y. M., & Alberts, D. S. (1997) · PubMed · Cited by 199 · see citing works
Self-citationCervical Cancer: Prevention, Diagnosis, and Therapeutics
Janicek, M. F., & Averette, H. E. (2001) · CA A Cancer Journal for Clinicians · doi:10.3322/canjclin.51.2.92 · Cited by 198 · see citing works
Castle, P. E., & Giuliano, A. R. (2003) · JNCI Monographs · doi:10.1093/oxfordjournals.jncimonographs.a003478 · Cited by 197 · see citing works
Cancer Chemoprevention: Progress and Promise
Lippman, S. M., Lee, J. J., & Sabichi, A. L. (1998) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/90.20.1514 · Cited by 194 · see citing works
ZYC101a for Treatment of High-Grade Cervical Intraepithelial Neoplasia
García, F., Petry, K. U., Muderspach, L. I., et al. (2004) · Obstetrics and Gynecology · doi:10.1097/01.aog.0000110246.93627.17 · Cited by 188 · see citing works
The role of diet and nutrition in cervical carcinogenesis: A review of recent evidence
García-Closas, R., Castellsagué, X., Bosch, F. X., et al. (2005) · International Journal of Cancer · doi:10.1002/ijc.21193 · Cited by 185 · see citing works
“Results of this trial are consistent with a previous and more powerful trial evaluating the effect of all-trans-retinoic acid, showing an increase in CIN2 but not CIN3 regression rate in the intervention group.(45) Short follow-up (12 weeks) and small sample size (38 subjects in each arm) were the main drawbacks of th…”
ResultLoopik, D. L., Bentley, H. A., Eijgenraam, M. N., IntHout, J., Bekkers, R. L. M., & Bentley, J. R. (2021) · Journal of Lower Genital Tract Disease · doi:10.1097/lgt.0000000000000604 · Cited by 190 · see citing works
Retinoic Acid Actions through Mammalian Nuclear Receptors
Huang, P., Chandra, V., & Rastinejad, F. (2013) · Chemical Reviews · doi:10.1021/cr400161b · Cited by 167 · see citing works
Cancer Prevention: From 1727 to Milestones of the Past 100 Years
Lippman, S. M., & Hawk, E. T. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-1750 · Cited by 148 · see citing works
Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine
Ferreira, R., Napoli, J., Enver, T., Bernardino, L., & Ferreira, L. (2020) · Nature Communications · doi:10.1038/s41467-020-18042-2 · Cited by 138 · see citing works
New agents for cancer chemoprevention
Keiloff, G. J., Boone, C. W., Crowell, J. A., Steele, V. E., Lubet, R. A., Doody, L. A., Malone, W. F., Hawk, E. T., & Sigman, C. C. (1996) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240630703 · Cited by 135 · see citing works
Advances in the Development of Retinoids as Chemopreventive Agents
Lippman, S. M., & Lotan, R. (2000) · Journal of Nutrition · doi:10.1093/jn/130.2.479s · Cited by 131 · see citing works
Tumor-suppressive activity of retinoic acid receptor-β in cancer
Xu, X.-C. (2006) · Cancer Letters · doi:10.1016/j.canlet.2006.11.019 · Cited by 127 · see citing works
Meyskens, F. L., Gerner, E. W., Emerson, S. S., Pelot, D., Durbin, T. E., Doyle, K. J., & Lagerberg, W. (1998) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/90.16.1212 · Cited by 125 · see citing works
Self-citationRetinoids in biological control and cancer
Fields, A. L., Soprano, D., & Soprano, K. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21530 · Cited by 116 · see citing works
“…epithelium of chronic smokers [Misset et al., 1986; Pastorino et al., 1993], skin premalignant lesions [Greenberg et al., 1990; Tangrea et al., 1992; Moon et al., 1997], cervical neoplasia [Meyskens et al., 1994; Braud et al., 2002], and several other precancer conditions [De Palo et al., 1995].”
BackgroundChoi, Y. J., Hur, S. Y., Kim, T. J., Hong, S. R., Lee, J. K., Cho, C., Park, K. S., Woo, J. W., Sung, Y. C., Suh, Y. S., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1513 · Cited by 120 · see citing works
Nutrition and cervical neoplasia
Potischman, N. A., & Brinton, L. A. (1996) · Cancer Causes & Control · doi:10.1007/bf00115643 · Cited by 120 · see citing works
An updated natural history model of cervical cancer: derivation of model parameters
Campos, N. G., Burger, E. A., Sy, S., Sharma, M., Schiffman, M., Rodriguez, A. C., Hildesheim, A., Herrero, R., & Kim, J. J. (2014) · American Journal of Epidemiology · doi:10.1093/aje/kwu159 · Cited by 116 · see citing works
Connexins as targets for cancer chemoprevention and chemotherapy
King, T. J., & Bertram, J. S. (2005) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2005.08.012 · Cited by 114 · see citing works
The Retinoids and Cancer Prevention Mechanisms
Dragnev, K. H., Rigas, J. R., & Dmitrovsky, E. (2000) · The Oncologist · doi:10.1634/theoncologist.5-5-361 · Cited by 112 · see citing works
Methylation and silencing of the retinoic acid receptor-β2 gene in cervical cancer
Иванова, Т. А., Petrenko, A. A., Gritsko, T., et al. (2002) · BMC Cancer · doi:10.1186/1471-2407-2-4 · Cited by 105 · see citing works
“RA treatment has inhibited transformation of human keratinocytes by HPV-16 [18] and has enhanced regression of cervical moderate dysplasia [19].”
BackgroundKing, T. J., Fukushima, L. H., Hieber, A., Shimabukuro, K., Sakr, W., & Bertram, J. S. (2000) · Carcinogenesis · doi:10.1093/carcin/21.6.1097 · Cited by 106 · see citing works
Dynamic behavioural interpretation of cervical intraepithelial neoplasia with molecular biomarkers
Baak, J. P. A., Kruse, A.-J., Robboy, S. J., et al. (2006) · Journal of Clinical Pathology · doi:10.1136/jcp.2005.027839 · Cited by 96 · see citing works
Epidermal growth factor receptor tyrosine kinase inhibitors as potential cancer chemopreventives.
Kelloff, G. J., Fay, J. R., Steele, V. E., Lubet, R., Boone, C. W., Crowell, J. A., & Sigman, C. C. (1996) · PubMed · Cited by 96 · see citing works
Molecular cancer prevention: Current status and future directions
Maresso, K. C., Tsai, K. Y., Brown, P. H., Szabo, E. M., Lippman, S. M., & Hawk, E. T. (2015) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21287 · Cited by 92 · see citing works
Obermair, A., Bancher‐Todesca, D., Bilgi, S., Kaider, A., Kohlberger, P., Müllauer-Ertl, S., Leodolter, S., & Gitsch, G. (1997) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/89.16.1212 · Cited by 83 · see citing works
Madireddi, M. T., Dent, P., & Fisher, P. B. (2000) · Journal of Cellular Physiology · doi:10.1002/1097-4652(200010)185:1 · Cited by 46 · see citing works
Differential Expression of Nuclear Retinoid Receptors in Normal and Malignant Prostates
Lotan, Y., Xu, X., Shalev, M., et al. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.1.116 · Cited by 84 · see citing works
Abu, J., Batuwangala, M., Herbert, K. E., & Symonds, P. R. (2005) · The Lancet Oncology · doi:10.1016/s1470-2045(05)70319-3 · Cited by 84 · see citing works
Retinoids and chemoprevention: Clinical and basic studies
Lippman, S. M., Heyman, R. A., Kurie, J. M., Benner, S. E., & Hong, W. K. (1995) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240590802 · Cited by 82 · see citing works
Antioxidant nutrients: associations with persistent human papillomavirus infection.
Giuliano, A. R., Papenfuss, M. R., Nour, M., et al. (1997) · PubMed · Cited by 81 · see citing works
Chen, X., Wang, R., Zhao, X., Wei, Y., Hu, M., Wang, Y.-S., Zhang, X.-W., Zhang, R., Zhang, L., Yao, B., et al. (2006) · Carcinogenesis · doi:10.1093/carcin/bgl069 · Cited by 79 · see citing works
Childers, J. M., Chu, J. Y., Voigt, L. F., et al. (1995) · PubMed · Cited by 79 · see citing works
Self-citationGonzalez, C. A., Travier, N., Luján‐Barroso, L., Castellsagué, X., Bosch, F. X., Roura, E., Bueno-de-Mesquita, H. B., Palli, D., Boeing, H., Pala, V. M., et al. (2010) · International Journal of Cancer · doi:10.1002/ijc.25679 · Cited by 77 · see citing works
Carotenoids and Retinoids: A Review of Research, Clinical, and Public Health Applications
Hinds, T. S., WEST, W. L., & Knight, E. M. (1997) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1997.tb04336.x · Cited by 75 · see citing works
García, F., Cornelison, T. L., Nuño, T., et al. (2014) · Gynecologic Oncology · doi:10.1016/j.ygyno.2013.12.034 · Cited by 74 · see citing works
Self-citationSeewaldt, V. L., Kim, J., Caldwell, L. E., Johnson, B. S., Swisshelm, K. L., & Collins, S. (1997) · PubMed · Cited by 74 · see citing works
The failure of cancer chemoprevention
Potter, J. D. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu063 · Cited by 72 · see citing works
“One topical application study of retinoids suggested effectiveness against cervical lesions (25), another did not (26) and an oral study was null (27).”
BackgroundOral diindolylmethane (DIM): Pilot evaluation of a nonsurgical treatment for cervical dysplasia
Priore, G. D., Gudipudi, D. K., Montemarano, N., et al. (2009) · Gynecologic Oncology · doi:10.1016/j.ygyno.2009.10.060 · Cited by 71 · see citing works
Rock, C. L., Michael, C. W., Reynolds, R. K., & Ruffin, M. T. (2000) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(99)00073-6 · Cited by 68 · see citing works
“Data from the Arizona group [42,76–81] and others [82] suggested that the natural history of cervical dysplasia can be altered by retinoids applied topically.”
BackgroundInfluentialVaginal drug delivery for the localised treatment of cervical cancer
Major, I., & McConville, C. (2017) · Drug Delivery and Translational Research · doi:10.1007/s13346-017-0395-2 · Cited by 69 · see citing works
“However, there was no significant difference between the two arms in the CIN III patients, demonstrating that the localised delivery of atRA is effective against moderate CIN but not severe CIN [94].”
BackgroundBioactive carotenoids: potent antioxidants and regulators of gene expression
Hix, L. M., Lockwood, S. F., & Bertram, J. S. (2004) · Redox Report · doi:10.1179/135100004225005967 · Cited by 65 · see citing works
Trump, D. L., Smith, D. C., Stiff, D. D., Adedoyin, A. B., Day, R., Bahnson, R. R., Hofacker, J., & Branch, R. A. (1997) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s002800050582 · Cited by 64 · see citing works
Keefe, K. A., Schell, M. J., Brewer, C., et al. (2001) · PubMed · Cited by 64 · see citing works
Self-citationOridate, N., Lotan, D., Mitchell, M. F., et al. (1995) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240590911 · Cited by 63 · see citing works
Dragnev, K. H., Pitha, I., Ma, Y., Petty, W. J., Sekula, D., O’Sullivan-Murphy, B., Rendi, M. H., Suh, N., Desai, N. B., Sporn, M. B., et al. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-03-0271 · Cited by 62 · see citing works
“A retinoid role in clinical cancer chemoprevention was supported by results from treatment of preneoplastic lesions such as oral leukoplakia (8), cervical dysplasia (9), and xeroderma pigmentosum (10).”
BackgroundDesravines, N., Miele, K., Carlson, R., Chibwesha, C. J., & Rahangdale, L. (2020) · Gynecologic Oncology Reports · doi:10.1016/j.gore.2020.100608 · Cited by 58 · see citing works
Campos, N. G., Tsu, V., Jeronimo, J., Mvundura, M., Lee, K., & Kim, J. J. (2015) · Papillomavirus Research · doi:10.1016/j.pvr.2015.05.003 · Cited by 56 · see citing works
Dragnev, K. H., Stover, D. E., & Dmitrovsky, E. (2003) · CHEST Journal · doi:10.1378/chest.123.1_suppl.60s · Cited by 55 · see citing works
Strategies for identification and clinical evaluation of promising chemopreventive agents.
Gj, K., Et, H., Crowell, J. A., et al. (1996) · PubMed · Cited by 55 · see citing works
Alvarez, R. D., Conner, M., Weiss, H. L., Klug, P. M., Niwas, S., Manne, U., Bacus, J. V., Kagan, V., Sexton, K. C., Grubbs, C. J., et al. (2003) · PubMed · Cited by 53 · see citing works
Schiffman, M. H., & Burk, R. D. (1997) · Springer eBooks · doi:10.1007/978-1-4899-0036-4_33 · Cited by 60 · see citing works
Efficiency of All-Trans Retinoic Acid on Gastric Cancer: A Narrative Literature Review
Bouriez, D., Giraud, J., Gronnier, C., & Varon, C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113388 · Cited by 52 · see citing works
“Moreover, many studies show that retinoids can inhibit growth of precancerous lesions, such as cervix dysplasia [53] and leukoplakia [54], and of several solid tumors, such as mammary cancer [20], lymphoma [21], head and neck cancer [22], melanoma [23], and GC [19], demonstrating that RAs have a differentiation proper…”
BackgroundChoi, C. H., Lee, K.-M., Choi, J., et al. (2007) · Cancer Letters · doi:10.1016/j.canlet.2007.03.015 · Cited by 52 · see citing works
“In cervical cancer, the RAR-b gene is of particular interest because retinoic acid inhibits transformation of human keratinocytes by HPV-16 [29] and results in regression of moderate cervical dysplasia [30].”
BackgroundPrevention of cervical intraepithelial neoplasia and cervical cancer
Meyskens, F. L., & Manetta, A. (1995) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/62.6.1417s · Cited by 52 · see citing works
Self-citationRecent advances in cancer chemoprevention, with emphasis on breast and colorectal cancer
DeCensi, A., & Costa, A. (2000) · European Journal of Cancer · doi:10.1016/s0959-8049(00)00040-x · Cited by 51 · see citing works
Seewaldt, V. L., Dietze, E. C., Johnson, B. S., Collins, S., & Parker, M. B. (1999) · PubMed · Cited by 51 · see citing works
Meyskens, F. L., Curt, G. A., Brenner, D. E., et al. (2011) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-09-0014 · Cited by 50 · see citing works
“pithelial neoplasia (IEN) and cervical IEN (3, 4), and (at a high dose) in the prevention of second head and neck malignancies (5) were positive, these initial "proof of”
BackgroundInfluentialSelf-citationWang, Y., Fang, M., Liao, J., et al. (2003) · PubMed · Cited by 50 · see citing works
Heatley, M. K. (2002) · Histopathology · doi:10.1046/j.1365-2559.2002.01365.x · Cited by 49 · see citing works
Fenretinide: a prototype cancer prevention drug
Malone, W. F., Perloff, M., Crowell, J. A., Sigman, C. C., & Higley, H. R. (2003) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.12.11.1829 · Cited by 50 · see citing works
“Considerable efficacy has been demonstrated with these agents in the treatment of precancerous intraepithelial neoplasia, such as oral leukoplakia [6] and cervical dysplasia [7], in the prevention of second primary tumours of the head and neck [8] and skin cancers in xeroderma pigmentosa patients or those with a high…”
BackgroundPapadimitrakopoulou, V. A., Shin, D. M., & Hong, W. K. (1996) · Cancer and Metastasis Reviews · doi:10.1007/bf00049487 · Cited by 48 · see citing works
Shalinsky, D. R., Bischoff, E. D., Gregory, M. L., Gottardis, M. M., Hayes, J. S., Lamph, W. W., Heyman, R. A., Shirley, M. A., Cooke, T. A., & Davies, P. J. (1995) · PubMed · Cited by 48 · see citing works
Ovarian cancer screening. The role of ultrasound in early detection
Karlan, B. Y., & PLATT, L. D. (1995) · Cancer · doi:10.1002/1097-0142(19951115)76:10+ · Cited by 39 · see citing works
Liu, T., Soong, S.-J., Alvarez, R. D., et al. (1995) · PubMed · Cited by 46 · see citing works
Seewaldt, V. L., Caldwell, L. E., Johnson, B. S., Swisshelm, K. L., Collins, S. J., & Tsai, S. (1997) · Experimental Cell Research · doi:10.1006/excr.1997.3694 · Cited by 46 · see citing works
Angiogenesis in Vulvar Intraepithelial Neoplasia
Bancher‐Todesca, D., Obermair, A., Bilgi, S., Kohlberger, P., Kainz, C., Breitenecker, G., Leodolter, S., & Gitsch, G. (1997) · Gynecologic Oncology · doi:10.1006/gyno.1996.4582 · Cited by 46 · see citing works
Creek, K. E., Geslani, G. P., Batova, A., et al. (1995) · Advances in experimental medicine and biology · doi:10.1007/978-1-4899-0949-7_11 · Cited by 45 · see citing works
Kim, E. J., Kang, Y., Schaffer, B. S., et al. (2001) · Journal of Cellular Physiology · doi:10.1002/jcp.10045 · Cited by 44 · see citing works
“…support for the use of retinoids in clinical chemoprevention came from the successful use of these compounds for the treatment of premaligant lesions such as cervical dysplasia (Meyskens et al., 1994), xeroderma pigmentosum (Kraemer et al., 1988), and oral leukotplakia (Hong et al., 1986).”
BackgroundDFMO: Targeted risk reduction therapy for colorectal neoplasia
Laukaitis, C. M., & Gerner, E. W. (2011) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2011.09.007 · Cited by 43 · see citing works
Cyclin Proteolysis as a Retinoid Cancer Prevention Mechanism
Dragnev, K. H., Freemantle, S. J., Spinella, M. J., & Dmitrovsky, E. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb02724.x · Cited by 43 · see citing works
Rock, C. L., MOSKOWITZ, A., HUIZAR, B., Saenz, C. C., CLARK, J. T., Daly, T., Chin, H. G., Behling, C. A., & Ruffin, M. T. (2001) · Journal of the American Dietetic Association · doi:10.1016/s0002-8223(01)00286-3 · Cited by 42 · see citing works
DNA Methylation Changes in Cervical Cancers
Lü, Q., Ma, D., & Zhao, S. (2012) · Methods in molecular biology · doi:10.1007/978-1-61779-612-8_9 · Cited by 39 · see citing works
Epidemiology of HIV-Associated Malignancies
Maso, L. D., Serraino, D., & Franceschi, S. (2001) · Cancer treatment and research · doi:10.1007/978-1-4615-1601-9_1 · Cited by 39 · see citing works
Ruffin, M. T., Bailey, J. M., Normolle, D. P., et al. (2004) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.2148.13.12 · Cited by 37 · see citing works
“37% (8) and shown to be significantly more effective in treating cervical intraepithelial neoplasia (CIN) II than a placebo agent (9).”
BackgroundMethodResultInfluentialXu, X., Mitchell, M. F., Silva, E. G., et al. (1999) · PubMed · Cited by 35 · see citing works
Weiss, G. R., Liu, P. Y., Alberts, D. S., et al. (1998) · Gynecologic Oncology · doi:10.1006/gyno.1998.5204 · Cited by 35 · see citing works
“liver, and cervical carcinogenesis [8–16].”
Self-citationFrom Human Papillomavirus (HPV) Detection to Cervical Cancer Prevention in Clinical Practice
Lee, S., Vigliotti, J. S., Vigliotti, V. S., et al. (2014) · Cancers · doi:10.3390/cancers6042072 · Cited by 34 · see citing works
“However, since CIN 2 is not a true biologic entity but an equivocal diagnosis of precancer, in fact representing an admixture of HPV infection and precancerous changes and a range of observational variables [21], and since 19%–50% of the CIN2 and CIN3 lesions are self-reversible [20,21,83–85], it is extremely difficul…”
BackgroundMethodDietary carotenoids, connexins and cancer: what is the connection?
Bertram, J. S. (2004) · Biochemical Society Transactions · doi:10.1042/bst0320985 · Cited by 34 · see citing works
- Authors
- Meyskens, F. L., Surwit, E., Moon, T. E., Childers, J. M., Davis, J. R., Dorr, R. T., Johnson, C. S., & Alberts, D. S.
- Affiliations
- University of Arizona (US)
- Venue
- JNCI: Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 1994-04-06
- Volume
- 86
- Issue
- 7
- Pages
- 539-543
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2012603529
- Cited by
- 263
- References
- 20
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 8 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 5
- FWCI
- 15.77
- Type
- journal article
- Language
- en
- Open access
- green
- escholarship.org
- Licence
- cc-by
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Cancer Institute (CA40889, CA 27502, P01CA027502)
- Topics
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- cervical intraepithelial neoplasia, moderate dysplasia, severe dysplasia, all-trans retinoic acid, topical retinoids, chemoprevention, histological regression, vitamin A, cervical cancer prevention, local adverse reactions
- MeSH terms
- Administration, Intravaginal, Adult, Antineoplastic Agents, Biopsy, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms, Female, Humans, Remission Induction, Tretinoin, Logistic Models
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
