IGF-I biomarker testing in an ethical context

Annabelle Trojan, Beatriz H. Aristizabal, Lina M. Jay, Tatiana Castillo, Pedro J. Penagos, Ignacio Briceño, Jerzy Trojan

Abstract


As we have come to know, there is a connection between cancer biomarkers and genes, along with their susceptibility to a particular disease, all of which have an obvious impact on the clinical practice and development of genetic testing. In any cancer disease, the diagnosis and treatment should be related to the investigation of specific biomarkers (generally antigens and proteins) and their corresponding genes. The study of different antigens such as alpha-fetoprotein, insulin-like growth factor I (IGF-I), insulin-like growth factor II, vascular endothelial growth factor, and epidermal growth factor, as well as their presence in neoplastic cells have demonstrated that IGF-I is an essential target for gene testing and therapeutic purpose. An over-expression of the IGF-I gene in mature tissues is a sign of neoplastic processes, e.g. brain or breast malignancy. A lot of questions have arisen regarding the ethics of gene testing, particularly concerns on the selection of patients for specific growth hormone/insulin-like growth factor I (GHIIGF-I) testing. Evidently, our current society is involved in a process of geneticization – the redefinition of individuals in terms of genetic codes. As such, we should take extreme care when making ethical judgments based on “scientific evidence” derived from genetic testing (typically those involving different biomarkers such as DNA, RNA, chromosomes, and proteins) in relation to genetic abnormalities that could predict current or future diseases. In this situation, the understanding of bioethics is of utmost importance.

Keywords


cancer, biomarkers, IGF-I, gene testing, bioethics

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References


Trojan J, Uriel J, Deugnier MA, Gaillard J. Immunocy-tochemical quantitative study of alpha-fetoprotein in normal and neoplastic neural development. Dev Neurosci 1983–1984; 6(4–5): 251–259. doi: 10.1159/000112352.

Trojan J, Uriel J. (French) [Intracellular localisation of alpha-fetoprotein and serum albumin in the central nervous system of the rat during fetal and postnatal development]. CR Acad Sci Paris 1979; 289(15): 1157–1160.

Sandberg AC, Engberg C, Lake M, von Holst H, Sara VR. The expression of insulin-like growth factor I and insu-lin-like growth factor II genes in the human fetal and adult brain and in glioma. Neurosci Lett 1988; 93(1): 114–119. doi: 10.1016/0304-3940(88)90022-5.

Kiess W, Lee L, Graham DE, Greenstein L, Tseng LYH, et al. Rat C6 glial cells synthesize insulin-like growth factor I (IGF-I) and express IGF-I receptors and IGF-II/ mannose 6-phosphate receptors. Endocrinol 1989; 124(4): 1727–1736. doi: 10.1210/endo-124-4-1727.

Johnson TR, Trojan J, Rudin SD, Blossey BK, Ilan J, et al. Effects of actinomycin D and cycloheximide on transcript levels of IGF-I, actin, and albumin in hepatocyte primary cultures treated with growth hormone and insulin. Mol Reprod Dev 1991; 30(2): 95–99. doi: 10.1002/mrd.1080 300204.

Trojan J, Blossey BK, Johnson TR, et al. Loss of tumor-igenicity of rat glioblastoma directed by episome-based antisense cDNA transcription of insulin-like growth factor I. Proc Natl Acad Sci USA 1992; 89(11): 4874–4878. doi: 10.1073/pnas.89.11.4874.

Trojan J, Johnson TR, Rudin SD, Ilan J, Tykocinski ML, et al. Treatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor I RNA. Science 1993; 259(5091): 94–97. doi: 10.1126/science.8418502.

NCI Dictionary of Cancer Terms [Internet]. National Cancer Institute (US); 2015 [cited 2016]. Available from: http://www.cancer.gov/publications/dictionaries/cancer-terms.

Trojan J, Naval X, Johnson T, Lafarge-Frayssinet C, Hajeri-Germond M, et al. Expression of serum albumin and of alphafetoprotein in murine normal and neoplastic primitive embryonic structures of teratocarcinoma. Molec Reprod Dev 1995; 42 (4), 369-378. doi: 10.1002/mrd.10 80420402

Hu B, Niu X, Cheng L, Yang LN, Li Q, et al. Discovering cancer biomarkers from clinical samples by protein mi-croarrays. Proteomics Clin Appl 2015; 9(1–2): 98–110. doi: 10.1002/prca.201400094.

Trojan LA, Kopinski P, Wei MX, Ly A, Glogowska A, et al. IGF-I: From diagnostic to triple-helix gene therapy of solid tumors. Acta Biochim Pol 2002; 49(4): 979–990.

Verma M and Manne U. Genetic and epigenetic bi-omarkers in cancer diagnosis and identifying high risk populations. Critical Rev Oncol Hematol 2006; 60(1): 9–18. doi: l0.1016/j.critrevonc.2006.04.002.

Cruz Tapias PA, Villegas Gálvez VE, Ramírez Clavijo SR. Fundamento biológico y aplicación clínica de los marca-dores tumorales séricos (Spanish) [Biological basis and clinical application of serum tumor markers]. Rev Cienc Salud 2008; 6(2): 85–98.

Galvis-Jiménez JM, Curtidor H, Patarroyo MA, Monter-rey P, Ramírez Clavijo SR, et al. Mammaglobin peptide as a novel biomarker for breast cancer detection. Cancer Biol Ther 2013; 14(4): 327‒332. doi: 10.4161/cbt.23614.

Henry MR, Cho MK, Weaver MA, Merz JF. DNA pa-tenting and licensing. Science 2002; 297(5585): 1279. doi: 10.1126/science.1070899.

Baird P. Patenting and human genes. Perspect Biol Med 1998; 41(3): 391‒408. doi: 10.1353/pbm.1998.0061.

Poland SC. Genes, patents, and bioethics - Will history repeat itself? Kennedy Inst Ethics J 2000; 10(3): 265‒281. doi: 10.1353/ken.2000.0022.

Byk C. A map to a new treasure island: The human ge-nome and the concept of common heritage. J Med Philos 1998; 23(3): 234‒246. doi: 10.1076/jmep.23.3.234.2589.

Heller MA, Eisenberg RS. Can patents deter innovation? The anticommons in biomedical research. Science 1998; 280(5364): 698‒701. doi: 10.1126/science.280.5364.698.

Froesch ER, Schmid C, Schwander J, Zapf J. Actions of insulin-like growth factors. Annu Rev Physiol 1985; 47: 443‒467. doi: 10.1146/annurev.ph.47.030185.002303.

Han VK, D’Ercole AJ, Lund PK. Cellular localization of somatomedin (Insulin-like growth factor) messenger RNA in the human fetus. Science 1987; 236(4798): 193‒197. doi: 10.1126/science.3563497.

Trojan J, Uriel J. Localisation of alphafetoprotein (AFP) in murine teratocarcinoma. Biomedicine 1981; 34(3): 140‒146.

Chatel M, Bourg V. (French) [Intracerebral tumours]. Rev Prat 2004; 54(8): 889‒896.

Guha A, Mukherjee J. Advances in the biology of astro-cytomas. Curr Opin Neurol 2004; 17(6): 655‒662. doi: 10. 1097/00019052-200412000-00004.

Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, et al. Genetic pathways to glioblastoma: A popula-tion-based study. Cancer Res 2004; 64(19): 6892‒6899. doi: 10.1158/0008-5472.CAN-04-1337.

Wrensch M, Rice T, Miike R, McMillan A, Lamborn KR, et al. Diagnostic, treatment, and demographic factors in-fluencing survival in a population-based study of adult glioma patients in the San Francisco Bay Area. Neuro Oncol 2006; 8(1): 12‒26. doi: 10.1215/S1522851705000268.

Trojan J, Pan YX, Wei MX, Ly A,Shevelev A, et al. Methodology for anti-gene anti-IGF-I therapy of malignant tumours. Chemother Res Pract 2012(2012). doi: l0.1155/2012/721873.

Hajeri-Germond M, Naval J, Trojan J, Uriel J. The uptake of alpha-foetoprotein by C-1300 mouse neuroblastoma cells. Br J Cancer 1985; 51: 791‒797. doi: 10.1038 /bjc.1985.123.

Lafarge-Frayssinet C, Duc HT, Sarasin A, Anthony D, Guo Y, et al. Antisense IGF-I transferred into a rat hepa-toma cell line inhibits tumorigenesis by modulating MHC-I cell surface expression. Cancer Gene Ther 1997; 4(5): 276‒285.

Anthony DD, Pan YX, Wu SG, Shen F, Guo J. Ex vivo and in vivo IGF-I antisense RNA strategies for treatment of cancer in humans. In: Walden P, Trefzer U, Sterry W, Farzaneh F, Zambon P, (editors). Gene therapy of cancer. New York: Springer US; 1998. p. 27‒34. doi: 10.1007/978-1-4615-5357-1_5.

Trojan J, Duc HT, Upegui-Gonzalez LC, Hor F, Guo Y, et al. Presence of MHC-I and B-7 molecules in rat and hu-man glioma cells expressing antisense IGF-I mRNA. Neurosci Lett 1996; 212(1): 9‒12. doi: 10.1016/0304-394 0(96)12770-1.

Upegui-Gonzalez LC, Duc HT, Buisson Y, Arborio M, Lafarge-Frayssinet C, et al. Use of the IGF-I antisense strategy in the treatment of the hepatocarcinoma. In: Walden P, Trefzer U, Sterry W, Farzaneh F, Zambon P, (editors). Gene therapy of cancer. New York: Springer US; 1998. p. 35‒42. doi: 10.1007/978-1-4615-5357-1_6.

Kooijman R. Regulation of apoptosis by insulin-like growth factor (IGF)-I. Cytokine Growth Factor Rev 2006; 17(4): 305–323. doi: 10.1016/j.cytogfr.2006.02.002.

Riedel F, Götte K, Li M, Hörmann K, Grandis JR. Abro-gation of VEGF expression in human head and neck squamous cell carcinoma decreases angiogenic activity in vitro and in vivo. Int J Oncol 2003; 23(3): 577–583. doi: 10.3892/ijo.23.3.577.

Reardon DA, Quinn JA, Vredenburgh JJ, Gururangan S, Friedman AH, et al. Phase 1 trial of gefitinib plus sirolimus in adults with recurrent malignant glioma. Clin Cancer Res 2006; 12(3): 860–868. doi: 10.1158/1078-0432.CCR-05-2215.

Lassman AB, Rossi MR, Razier JR, Abrey LE, Lieberman FS, et al. Molecular study of malignant gliomas treated with epidermal growth factor receptor inhibitors: Tissue analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01. Clin Cancer Res 2005; 11(21): 7841–7850. doi: 10.1158/1078-0432.CCR-05-04 21.

Schlingensiepen KH, Jaschinski F, Lang SA, Moser C, Geissler EK, et al. Transforming growth factor-beta 2 gene silencing with trabedersen (AP 12009) in pancreatic cancer. Cancer Sci 2011; 102(6): 1193–1200. doi: 10.1111 /j.1349-7006.2011.01917.x.

Ostos H, Astaiza G, Garcia F, Bautista M, Rojas F. Dis-minución de la incidencia de defectos de cierre del tubo neural en el Hospital Universitario de Neiva: Posible efecto de la promoción del consumo de ácido fólico (Spanish) [Decreased incidence of defects of neural tube closure at the University Hospital of Neiva: Possible effect promotion of folic acid]. Biomédica 2000; 20(1): 18–24. doi: 10.7705/biomedica.v20i1.1043.

Trojan J, Cloix JF, Ardourel MY, Chatel M, Anthony DD. Insulin-like growth factor type I biology and targeting in malignant gliomas. Neurosci 2007; 145(3): 795–811. doi: 10.1016/j.neuroscience.2007.01.021.

Le Roith D, Bondy C, Yakar S, Liu JL, Butler A. The somatomedin hypothesis: 2001. Endocr Rev 2011; 22(1): 53–74. doi: 10.1210/edrv.22.1.0419.

Bermudez AJ, Salinas S. Recomendación sobre el uso de pruebas rápidas para TSH neonatal (Spanish) [Recommendation on the use of rapid tests for neonatal TSH]. Informe Quincenal-Epidemio Nac 2002; 7(7): 102–106.

Le Roith D. The insulin-like growth factor system. Exp Diabesity Res 2003; 4(4): 205–212. doi: 10.1155/EDR.20 03.205.

Baserga R. The insulin-like growth factor-I receptor as a target for cancer therapy. Expert Opin Ther Targets 2005; 9(4): 753–768. doi: 10.1517/14728222.9.4.753.

Adhami VM, Afaq F, Mukhtar H. Insulin-like growth factor-I axis as a pathway for cancer chemoprevention. Clin Cancer Res 2006; 12(19): 5611–5614. doi: 10.1158/ 1078-0432.CCR-06-1564.

Chen H, Mester T, Raychaudhuri N, et al. Teprotumumab, an IGF-1R blocking monoclonal antibody inhibits TSH and IGF-1 action in fibrocytes. J Clin Endocrinol Metab 2014; 99(9): E1635–1640. doi: 10.1210/jc.2014-1580.

Baserga R. Oncogenes and the strategy of growth factors. Cell 1994; 79(6): 927–930. doi: 10.1016/0092-8674(94)9 0023-X.

Pollak MN, Schernhammer ES, Hankinson SE. Insulin-like growth factors and neoplasia. Nat Rev Cancer 2004; 4: 505–518. doi:10.1038/nrc1387.

Kurmasheva RT, Houghton PJ. IGF-I mediated survival pathways in normal and malignant cells. Biochim Biophys Acta 2006; 1766(1): 1–22. doi:10.1016/j.bbcan.2006.05.003.

Baserga R, Sell C, Porcu P, Rubini M. The role of the IGF-I receptor in the growth and transformation of mammalian cells. Cell Prolif 1994; 27(2): 63–71. doi: 10. 1111/j.1365-2184.1994.tb01406.x.

Delaney CL, Cheng HL, Feldman EL. Insulin-like growth factor-I prevents caspase-mediated apoptosis in Schwarm cells. J Neurobiol 1999; 41(4): 540–548. doi: 10.1002/ (SICI)1097-4695(199912)41:4<540::AID-NEU9>3.0.CO;2-P.

Crowder RJ, Freeman RS. Glycogen synthase kinase-3β activity is critical for neuronal death caused by inhibiting phosphatidylinositol 3-kinase or Akt but not for death caused by nerve growth factor withdrawal. J Biol Chem 2000; 275(44): 34266–34271. doi: 10.1074/jbc.M006160200.

Mason JL, Ye P, Suzuki K, D’Ercole AJ, Matsushima GK. Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during primary demyelination. J Neurosci 2000; 20(15): 5703–5708.

Chrysis D, Calikoglu AS, Ye P, D’Ercole AJ. Insulin-like growth factor-I overexpression attenuates cerebellar apoptosis by altering the expression of Bcl family proteins in a developmentally specific manner. J Neurosci 2001; 21(5): 1481–1489.

Trojan J, Anthony DD. Antisense strategies in therapy of gliomas. Curr Signal Transduct Ther 2011; 6(3): 411–423. doi: 10.2174/157436211797483895.

Camirand A, Pollak M. Co-targeting IGF-1R and c-kit: Synergistic inhibition of proliferation and induction of apoptosis in H 209 small cell lung cancer cells. Br J Cancer 2004; 90(9): 1825–1829. doi: 10.1038/sj.bjc.660 1682.

Beckner ME, Gobbel GT, Abounader R, Burovic F, Ago-stino NR, et al. Glycolytic glioma cells with active gly-cogen synthase are sensitive to PTEN and inhibitors of PI3K and gluconeogenesis. Lab Invest 2005; 85(12): 1457–1470. doi: 10.1038/labinvest.3700355.

Vignot S, Faivre S, Aguirre D, Raymond E. mTOR- tar-geted therapy of cancer with rapamycin derivatives. Ann Oncol 2005; 16(4): 525–537. doi: 10.1093/annonc/mdi113.

Patel S, Doble B, Woodgett JR. Glycogen synthase kinase-3 in insulin and Wnt signalling: A double-edged sword? Biochem Soc Trans 2004; 32(5): 803–808. doi: 10.1042/BST0320803.

Jiang R, Mircean C, Shmulevich I, Cogdell D, Jia Y, et al. Pathway alterations during glioma progression revealed by reverse phase protein lysate arrays. Proteomics 2006; 6(10): 2964–2971. doi: 10.1002/pmic.200500555.

Hutterer M, Gunsilius E, Stockhammer G. Molecular therapies for malignant glioma. Wien Med Wochenschr 2006; 156(11): 351–363. doi: 10.1007/s10354-006-0308 -3.

Grossman SA, Alavi JB, Supko JG, Carson KA, Priet R, et al. Efficacy and toxicity of the antisense oligonucleotide aprinocarsen directed against protein kinase C-α delivered as a 21-day continuous intravenous infusion in patients with recurrent high-grade astrocytomas. Neuro Oncol 2005; 7(1): 32–40. doi: 10.1215/S1152851703000353.

Sachdev D, Yee D. Disrupting insulin-like growth factor signaling as a potential cancer therapy. Mol Cancer Ther 2007; 6(1): 1–12. doi: 10.1158/1535-7163.MCT-06-0080.

Ardourel M, Blin M, Moret JL, Dufour T, Duc HT, et al. A new putative target for antisense gene therapy of glioma: Glycogen synthetase. Cancer Biol Ther 2007; 6(5): 719–723. doi: 10.4161/cbt.6.5.4232.

Goudar RK, Shi Q, Hjelmeland MD, Keir ST, McLendon RE, et al. Combination therapy of inhibitors of epidermal growth factor receptor/vascular endothelial growth factor receptor 2 (AEE788) and the mammalian target of rapamycin (RAD001) offers improved glioblastoma tumor growth inhibition. Mol Cancer Ther 2005; 4(1): 101–112.

Zhou X, Ren Y, Moore L, Mei M, You Y, et al. Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status. Lab Invest 2010; 90: 144–155. doi: 10.1038/labinvest.2009.126.

Premkumar DR, Arnold B, Jane EP, Pollack IF. Synergis-tic interaction between 17-AAG and phosphatidylinositol 3-kinase inhibition in human malignant glioma cells. Mol Carcinog 2006; 45(1): 47–59. doi: 10.1002/mc.20152.

Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 2003; 3: 11–22. doi: 10.1038 /nrc969.

Sanson M, Laigle-Donadey F, Benouaich-Amiel A. Molecular changes in brain tumours: Prognostic and therapeutic impact. Curr Opin Oncol 2006; 18(6): 623–630. doi: 10.1097/01.cco.0000245322.11787.72.

Ertl DA, Gleiss A, Sagmeister S, Haeusler G. Determining the normal range for IGF-I, IGFBP-3, and ALS: New reference data based on current internal standards. Wien Med Wochenschr 2014; 164 (17–18): 343–352. doi: 10.10 07/s10354-014-0299-4.

Trojan J, Briceno I. IGF-I antisense and triple-helix gene therapy of glioblastoma. In: A. Pantar “Evolution of the molecular biology of brain tumors and the therapeutic implications”‏. Ed. InTech, Vienna, Riyeka, 2013, Ch. 5, pp 149-166. (ISBN: 980-953-307-743-2)

Vadgama JV, Wu Y, Datta G, Khan H, Chillar R. Plasma insulin-like growth factor-I and serum IGF-binding protein 3 can be associated with the progression of breast cancer, and predict the risk of recurrence and the probability of survival in African American and Hispanic women. Oncol 1999; 57(4): 330–340. doi: 10.1159/000 012052.

Campbell MJ, Woodside JV, Secker-Walker J, Titcomb A, Leathem AJC. IGF status is altered by tamoxifen in patients with breast cancer. Mol Pathol 2001; 54(5): 307– 310. doi: 10.1136/mp.54.5.307.

Eppler E, Zapf J, Bailer N, Falkmer UG, Falkmer S, et al. IGF-I in human breast cancer: Low differentiation stage is associated with decreased IGF-I content. Eur J Endocrinol 2002; 146: 813–821. doi: 10.1530/eje.0.1460813.

Wolk A, Anderson SO, Mantzoros CS, Trichopoulos D, Adami HO. Can measurements of IGF-I and IGFBP-3 improve the sensitivity of prostate cancer screening? Lancet 2000; 356(9245): 1902–1903. doi: 10.1016/S0140-6736(00)03266-9.

Trojan J, Kopinski P, Drewa T, Powierska-Czarny J, Pacholska J, et al. Immunogenotherapy of prostate cancer. Urol Pol 2003; 56(2): 7–11.

Mishra L, Bass B, Ooi BS, Sidawy A, Korman L, et al. Role of insulin-like growth factor-I (IGF-I) receptor, IGF-I, and IGF binding protein-2 in human colorectal cancers. Growth Horm IGF Res 1998; 8(6): 473–479. doi: 10.1016/S1096-6374(98)80300-6.

Kopinski P, Ly A, Trojan J. Antisense therapies in oncology. In: A. Ly & D. Khayat “About cancer in Africa”. Ed. INCa, Paris, 2006, pp 659-671. (ISBN: 978-2-7246-1172-4)

Pitts TM, Tan AC, Kulikowski GN, et al. Development of an integrated genomic classifier for a novel agent in col-orectal cancer: approach to individualized therapy in early development. Clin Cancer Res. 2010; 16(12): 3193- 204. doi: 10.1158/1078-0432.CCR-09-3191.

Lee DY, Kim SJ, Lee YC. Serum insulin-like growth fa-ctor (IGF)-I and IGF-binding proteins in lung cancer patients. J Korean Med Sci 1999; 14(4): 401–404. doi: 10.3346/jkms.1999.14.4.401.

Martenka J, Plato M, Kopiński P, Soja J, Szczeklik J, et al. (Polish) [Studies on insulin-like growth factor-I expression in human lower airways]. Pol Merkur Lekarski 2005; 19(113): 621–624.

Upegui-Gonzalez LC, Trojan LA, Ly A, François J-C, Przewlocki R, et al. Antisense and triple-helix strategies in basic and clinical research: Challenge for gene therapy of tumors expressing IGF-I. In: D. LeRoith, W. Zumkeller, RC. Baxter. “ Insulin like-Growth Factor I ”. Ed. Landes Bioscience/ Eurekah & Kluwer Academic/Plenum Publishers, New York, 2003, Ch. 22, pp 357-366. (ISBN: 1-58706-120-1)

Zumkeller W, Westphal M. The IGF/IGFBP system in CNS malignancy. Mol Pathol 2001; 54: 227–229. doi:10.1136/mp.54.4.227.

Giovannucci E. Insulin-like growth factor-I and binding protein-3 and risk of cancer. Horm Res Paediatr 1999; 51(Suppl 3): 34–41. doi: 10.1159/000053160.

Yu H, Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 2000; 92(18): 1472–1489. doi: 10.1093/jnci/92.18.1472.

Kopczak A, Stalla GK, Uhr M, Lucae S, Hennings J, et al. IGF-I in major depression and antidepressant treatment response. Eur Neuropsychopharmacol 2015; 25(6): doi: 10.1016/j.euroneuro.2014.12.013.

Vicente M. Avances en ingeniería genética (Spanish). Consejo Superior de Investigaciones Científicas Madrid, Spain; 1994.

Weinberg SL. Patient education as a part of critical care. Heart Lung 1974; 3(1): 47–48.

Mayr E. Weismann and evolution. J Hist Biol 1985; 18(3): 295–329. doi: 10.1007/BF00138928.

Yockey HP. Comments on “Let there be life; Thermody-namic reflections on biogenesis and evolution” by Avshalom C. Elitzur. J Theor Biol 1995; 176(3): 349–355. doi: 10.1006/jtbi.1995.0204.

Darwin C. The descent of man, and selection in relation to sex. Rev. ed., New York: Merrill and Baker; 1874. doi: 10.5962/bhl.title.54341.

Crick FH. The Croonian lecture, 1996: The genetic code. Proc R Soc Lond B Biol Sci 1967; 167(1009): 331–347.

Depew DJ, Weber BH. Evolution at a crossroads: The new biology and the new philosophy of science. Cam-bridge MA, US: MIT Press; 1985.

Monod J. Chance and necessity: An essay on the natural philosophy of modern biology. New York: Vintage Books; 1972.

Rubenstein JL, Nicolas JF, Jacob F. Construction of a retrovirus capable of transducing and expressing genes in multipotential embryonic cells. Proc Natl Acad Sci USA 1984; 81(22): 7137–7140. doi: 10.1073/pnas.81.22.7137.

Weintraub H, Izant JG, Harland RM. Anti-sense RNA as a molecular tool for genetic analysis. Trends Genet 1985; 1: 22–25. doi: 10.1016/0168-9525(85)90010-1.

Hélène C. Control of oncogene expression by antisense nucleic acids. Eur J Cancer 1994; 30A(11): 1721–1726.

Sharp PA. RNA interference—2001. Genes Dev 2001; 15: 485–490. doi: 10.1101/gad.880001.

Anderson WF, Blaese RM, Culver K. Points to consider response with clinical protocol, July 6, 1990. Hum Gene Ther 2008; 1(3): 331–362. doi: 10.1089/hum.1990.1.3-331.

Ferrari G, Rossini S, Nobili N, Maggioni D, Garofalo A, et al. Transfer of the ADA gene into human ADA-deficient T lymphocytes reconstitutes specific immune functions. Blood 1992; 80(5): 1120–1124.

Pulkkanen KJ, Yla-Herttuala S. Gene therapy for malignant glioma: Current clinical status. Mol Ther 2005; 12(4): 585–598.

Johnson TR, Trojan J, Rudin SD, Ilan Ju, Tykocinski ML et al. Evoking an immune response to glioblastoma cells transfected with episome based plasmid expressing anti-sense transcripts to insulin like growth factor I. In: AJ. Levine & H.H. Schmidek “Molecular genetics of nervous system tumours”. Ed. John Wiley & Sons, Inc., New York, 1993, pp 387-400. (ISBN: 0471561797)

Holtzman NA. Promoting safe and effective genetic tests in the United States: Work of the task force on genetic testing. Clin Chem 1999; 45(5): 732–738.

Pergament E. New molecular techniques for chromosome analysis. Best Pract Res Clin Obstet Gynaecol 2000; 14(4): 677–690. doi: 10.1053/beog.1999.0104.

Hoedemaekers R, Ten Have H. Genetic health and genetic disease. In: Launis V, Pietarinen J, Räikkä J, (editors). Genes and morality: New essays. Ed. Amsterdam-Atlanta GA: Rodopi BV; 1999. p. 121–143.

Ensenauer RE, Reinke SS, Ackerman MJ, Tester DJ, Whiteman DAH, et al. Primer on medical genomics Part VIII: Essentials of medical genetics for the practicing physician. Mayo Clin Proc 2003; 78(7): 846–857. doi: 10.4065/78.7.846.

Wideroff L, Freedman AN, Olson L, Klabunde CN, Davis W, et al. Physician use of genetic testing for cancer sus-ceptibility: Results of a national survey. Cancer Epidemiol Biomarkers Prev 2003; 12(4): 295–303.

Snow K. The growing impact of genetics on health care: Do we have appropriate educational resources? Mayo Clin Proc 2001; 76(8): 769–771. doi: 10.1016/S0025-619 6(11)63218-7.

Pagon RA, Pinsky L, Beahler CC. Online medical genetics resources: A US perspective. BMJ 2001; 322: 1035– 1037. doi: 10.1136/bmj.322.7293.1035.

Glazier AM, Nadeau JH, Aitman TJ. Finding genes that underlie complex traits. Science 2002; 298(5602): 2345– 2349. doi: 10.1126/science.1076641.

Grady WM. Genetic testing for high risk colon cancer patients. Gastroenterol 2003; 124(6): 1574–1594. doi: 10. 1016/S0016-5085(03)00376-7.

Saleh N, Moutereau S, Azulay JP, Verny C, Simonin C, et al. High insulin like growth factor I is associated with cognitive decline in Huntington disease. Neurology 2010; 75 (1): 57–63. doi: 10.1212/WNL.0b013e3181e62076.

Parente Pereira AC, McQuillin A, Puri V, Anjorin A, Bass N, et al. Genetic association and sequencing of the insu-lin-like growth factor 1 gene in bipolar affective disorder. Am J Med Genet B Neuropsychiatr Genet 2011; 156(2): 177–187. doi: 10.1002/ajmg.b.31153.

Bondy CA, Werner H, Roberts CT Jr, LeRoith D. Cellular pattern of insulin-like growth factor-I (IGF-I) and type I IGF receptor gene expression in early organogenesis: Comparison with IGF-II gene expression. Mol Endocrinol 1990; 4(9): 1386–1398. doi: 10.1210/mend-4-9-13 86.

Love S, Louis DN, Ellison DW. Greenfield’s neuropathology. 8th ed. Florida, USA: CRC Press; 2008. p. 521.

Sturm MA, Conover CA, Pham H, Rosenfeld RG. Insu-lin-like growth factor receptors and binding protein in rat neuroblastoma cells. Endocrinol 1989; 124(1): 388–396. doi: 10.1210/endo-124-1-388.

Trojan J, Johnson TR, Rudin SD, Blossey BK, Kelley KM, et al. Gene therapy of murine teratocarcinoma: Separate functions for insulin-like growth factors I and II in immunogenicity and differentiation. Proc Natl Acad Sci USA 1994; 91(13): 6088–6092. doi: 10.1073/pnas.91.13.6088.

Trojan J. (French) [Expression of neuro-ectoblast in mu-rine teratocarcinomas: Electron-microscopic and im-munocytochemical studies, applications in embryology and in tumor pathology of central nervous system]. Bull Inst Pasteur 1984; 83: 335–385.

Obrepalska-Steplowska A, Kedzia A, Trojan J, Goździc-ka-Józefiak A. Analysis of coding and promoter sequences of the IGF-I gene in children with growth disorders presenting with normal level of growth hormone. J Pediatr Endocrinol Metab 2003; 16(9): 1267–1275. doi: 10.1515/ JPEM.2003.16.9.1267.

Zumkeller W. IGFs and IGF-binding proteins as diagnos-tic markers and biological modulators in brain tumors. Expert Rev Mol Diagn 2002; 2(5): 473–477. doi: 10.1586/14737159.2.5.473.

Trojan J, Pan YX, Wei MX, Ly A, Shevelev A, et al. Methodology for anti-gene anti-IGF-I therapy of malignant tumours. Chemother Res Pract 2012; 2012(2012). doi: 10.1155/2012/721873.

Sussenbach JS, Steenbergh PH, Holthuizen P. Structure and expression of the human insulin-like growth factor genes. Growth Regul 1992; 2(1): 1–9.

Caliebe J, Broekman S, Boogaard M, Bosch CAJ, Ruiv-enkamp CAL, et al. IGF1, IGF1R and SHOX mutation analysis in short children born small for gestational age and short children with normal birth size (idiopathic short stature). Horm Res Paediatr 2012; 77(4): 250–260. doi: 10.1159/000338341.

Wit JM. Diagnosis and management of disorders of IGF-I synthesis and action. Pediatr Endocrinol Rev 2011; 9(Suppl 1): 538–540.

Metlapally R, Ki CS, Li YJ, Tran-Viet KN, Abbott D, et al. Genetic association of insulin-like growth factor-1 polymorphisms with high-grade myopia in an international family cohort. Invest Ophtalmol Vis Sci 2010; 51(9): 4476–4479. doi: 10.1167/iovs.09-4912.

Cao Y, Lindström S, Schumacher F, Stevens VL, Albanes D, et al. Insulin-like growth factor pathway genetic pol-ymorphisms, circulating IGF1 and IGFBP3, and prostate cancer survival. J Natl Cancer Inst 2014; 106(6): dju085. doi: 10.1093/jnci/dju085.

Gu F, Schumacher FR, Canzian F, Allen NE, Albanes D, et al. Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer. Cancer Epidemiol Biomarkers Prev 2010; 19(11): 2877–2887. doi: 10.1158/10 55-9965.EPI-10-0507.

Soerensen M, Dato S, Tan Q, Thinggaard M, Kleindorp R, et al. Human longevity and variation in GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/ an-tioxidant pathway genes: Cross sectional and longitudinal studies. Exp Gerontol 2012; 47(5): 379–387.doi: 10.1016/j.exger.2012.02.010.

Gibbons JJ, Abraham RT, Yu K. Mammalian target of rapamycin: Discovery of rapamycin reveals a signaling pathway important for normal and cancer cell growth. Semin Oncol 2009; 36(Suppl 3): S3–S17. doi: 10.1053/j.seminoncol.2009.10.011.

Piro A, Tagarelli G, Lagonia P, Quattrone A, Tagarelli A. Archibald Edward Garrod and alcaptonuria: “Inborn errors of metabolism” revisited. Genet Med 2010; 12: 475–476, doi: 10.1097/GIM.0b013e3181e68843.

Koppenol WH, Bounds PL, Dang CV. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer 2011; 11(5): 325–337. doi: 10.1038/nrc 3038.

Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011; 144(5): 646–674. doi: 10.1016/j.ce ll.2011.02.013.

Parsons DW, Jones S, Zhang X, Lin JCH, Leary RJ, et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008; 321(5897): 1807–1812. doi: 10.1126/science.1164382.

Yan H, Parsons DW, Jin G, McLendon R, Rasheed A, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009; 360(8): 765–773. doi: 10.1056/NEJMoa0808710.

Johnston Rohrbasser LB. Genetic testing of the short child. Horm Res Paediatr 2011; 76(Suppl 3): 13–16. doi: 10.1159/000330141.

Backeljauw P, Bang P, Clayton PE, Geffner M, Woods KA. Diagnosis and management of primary insulin-like growth factor-I deficiency: Current perspectives and clinical update. Pediatr Endocrinol Rev 2010; 7(Suppl 1): 154–171.

Hahn M, Saeger HD, Schackert HK. Hereditary colorectal cancer: Clinical consequences of predictive molecular testing. Int J Colorectal Dis 1999; 14(4): 184–193. doi: 10.1007/s003840050210.

Weitzel JN. Genetic cancer risk assessment. Cancer 1999; 86(Suppl 11): 2483–2492. doi: 10.1002/(SICI)1097-0142 (19991201)86: 11+2483::AID-CNCR5>3.0.CO;2-4

Hadley DW, Jenkins J, Dimond E, Nakahara K, Grogan L, et al. Genetic counseling and testing in families with he-reditary nonpolyposis colorectal cancer. Arch Intern Med 2003; 163(5): 573–582. doi: 10.1001/archinte.163.5.573.

Beauchamp TL, Childress JF. Principles of biomedical ethics. 4th ed., New York: Oxford University Press; 1994.

Pellegrino ED. Ethics. JAMA 1995; 273(21): 1674–1676. doi: 10.1001/jama.1995.03520450044022.

Gould SJ. Message from a mouse: It takes more than genes to make a smart rodent, or high-IQ humans. Time 1999; 154(11): 42.

Tang TLP, Weatherford EJ. Perception of enhancing self-worth through service: The development of a Service Ethic Scale. J Soc Psychol 1998; 138(6): 734–743. doi: 10.1080/00224549809603258.

Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, et al. Effect of COMT Vall08/158 Met geno-type on frontal lobe function and risk of schizophrenia. Proc Natl Acad Sci USA 2001; 98(12): 6917–6922. doi: 10.1073/pnas.111134598.

Hamer DH. A linkage between DNA markers on the X chromosome and male sexual orientation. Science 1993; 261(5119): 321–327. doi: 10.1126/science.8332896.

Nelkin D, Andrews LB. Whose genes are they anyway? Chron High Educ 1999; 45: B6.

Lippman A. Prenatal genetic testing and screening: Constructing needs and reinforcing inequities. Am J Law Med 1991; 17(1–2): 15–50.

Lippman A. Led (astray) by genetic maps: The cartography of the human genome and health care. Soc Sci Med 1992; 35(12): 1469–1476. doi: 10.1016/0277-9536(92)90049-V.

Rothman BK. Genetic maps and human imaginations: The limits of science in understanding who we are. New York: WW Norton and Company; 1998.

Lupton D. Medicine as culture: Illness, disease and the body in Western societies, Part 2. London: Sage Pub-lications Ltd; 1994.

Levin DM, Solomon GF. The discursive formation of the body in the history of medicine. J Med Philos 1990; 15(5): 515–537. doi: 10.1093/jmp/15.5.515.

Temple LKF, McLeod RS, Gallinger S, Wright JG. Essays on science and society: Defining disease in the genomics era. Science 2001; 293(5531): 807–808. doi: 10.1126/science.1062938.

Green ED, Watson JD, Collins FS. Human Genome Pro-ject: Twenty-five years of big biology. Nature 2015; 526(7571): 29–31. doi: 10.1038/526029a.




DOI: http://dx.doi.org/10.30564/amor.v2i4.66

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