癌症研究历史经典回顾和热点寻踪（二）
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按照基因突变理论，癌症的启动是突变的结果，之后不断选择，最后导致肿瘤发生，然而，癌症的启动也有表遗传改变的解释。
1: Jaffe LF. Epigenetic theories of cancer initiation [J]. Adv Cancer Res. 2003, 90:209-30.
2: Prehn RT. Cancers beget mutations versus mutations beget cancers [J]. Cancer Res. 1994, 54(20):5296-300.
肿瘤干细胞假说的历史回顾：
约150年前，病理学家Virchow等认为肿瘤来源于发育过程中某些潜伏的胚胎残余组织，这种推测基于对胚胎发育和某些肿瘤例如畸胎瘤的相似性的观察。1961年Bruce等发现只有1－4%的鼠类淋巴瘤细胞可以在被移植动物的脾脏形成克隆，1973年McCulloch等发现只有不到1%的髓白血病细胞可以在体外形成克隆。1977年Hamburger等发现1000－5000个实体瘤细胞中仅有1个细胞可以在软琼脂中形成细胞克隆。随着这些研究结果不断出现，上世纪70年代Potter和Pierce等分别提出肿瘤是干细胞分化成熟被抑制的结果。直到1997年Dick实验室分离到急性髓白血病干细胞，肿瘤干细胞的研究才逐渐升温，至今研究人员已经分别从慢性髓白血病、胶质瘤和乳腺癌中分离到具有特定免疫表型的肿瘤干细胞。
1: Jordan CT, Guzman ML.Mechanisms controlling pathogenesis and survival of leukemic stem cells [J].Oncogene. 2004, 23(43):7178-87.
2: Messner HA, McCulloch EA.Interacting cell populations affecting granulopoietic colony formation by normal and leukemic human marrow cells [J].Blood. 1973, 42(5):701-10.
3: Hamburger AW, Salmon SE. Primary bioassay of human tumor stem cells [J].Science. 1977, 197(4302):461-3.
4: Potter VR.Phenotypic diversity in experimental hepatomas: the concept of partially blocked ontogeny. The 10th Walter Hubert Lecture [J].Br J Cancer. 1978, 38(1):1-23.
5: Pierce GB.Relationship between differentiation and carcinogenesis [J]. J Toxicol Environ Health. 1977, 2:1335-42.
6: Bonnet D, Dick JE.Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell [J].Nat Med. 1997, 3(7):730-7.
癌症干细胞最新研究进展：
1: Reya T, Morrison SJ, Clarke MF, et.al. Stem cells, cancer, and cancer stem cells [J]. Nature. 2001, 414(6859):105-11.
2: Dalerba P, Cho RW, Clarke MF. Cancer Stem Cells: Models and Concepts.
Annu Rev Med. 2006 Sep 26;
3: Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL, Wahl GM. Cancer Stem Cells--Perspectives on Current Status and Future Directions: AACR Workshop on Cancer Stem Cells. Cancer Res. 2006 Oct 1;66(19):9339-44. Epub 2006 Sep 21.
癌症的表型遗传修饰改变假说历史回顾
早期研究人员发现化学诱癌实验产生的肿瘤，如果停止使用致癌剂和/或促癌剂，相当一部分肿瘤会通过重新分化而自发消失。上世纪40年代年Furth发现卵巢细胞移植到脾脏可以自发癌变。60年代King和McKinnell等将青蛙的肾癌细胞核转移到正常卵细胞中，发现这种卵细胞依然可以发育成正常的蝌蚪。70年代，Mintz和Illmensee等发现将畸胎瘤细胞移植至正常同系动物的胚泡内，结果产生不长肿瘤的嵌合型小鼠。Howell等发现肿瘤细胞和正常细胞的融合产生的细胞失去恶性表型。基于上述发现，1979年Holliday首先提出表型遗传修饰改变假说。80年代Sachs等将白血病细胞向同系动物的早期胚胎移植，发现白血病细胞可参与正常动物血液系统的发育，动物发育成熟后各系血液细胞均可发现白血病细胞的基因标记。90年代McCullough等将肝癌细胞向同系成年动物肝组织移植，发现癌细胞可参与正常肝脏细胞的更新；最近研究发现致癌剂作用于间质细胞却可以产生实质细胞肿瘤。
1: King TJ, DiBerardino MA.Transplantation of nuclei from the frog renal adenocarcinoma. I. Development of tumor nuclear-transplant embryos [J]. Ann N Y Acad Sci. 1965, 126(1):115-26.
2: McKinnell RG, Deggins BA, Labat DD.Transplantation of pluripotential nuclei from triploid frog tumors [J].Science. 1969, 165(891):394-6.
3: Mintz B, Illmensee K.Normal genetically mosaic mice produced from malignant teratocarcinoma cells [J].Proc Natl Acad Sci U S A. 1975, 72(9):3585-9.
4: Illmensee K, Mintz B.Totipotency and normal differentiation of single teratocarcinoma cells cloned by injection into blastocysts [J]. Proc Natl Acad Sci U S A. 1976, 73(2):549-53.
5: Howell AN, Sager R.Tumorigenicity and its suppression in cybrids of mouse and Chinese hamster cell lines [J]. Proc Natl Acad Sci U S A. 1978, 75(5):2358-62.
6: Holliday R.A new theory of carcinogenesis. Br J Cancer. 1979, 40(4):513-22.
7: Gootwine E, Webb CG, Sachs L.Participation of myeloid leukaemic cells injected into embryos in haematopoietic differentiation in adult mice [J]. Nature. 1982, 299(5878):63-5.
8: McCullough KD, Coleman WB, Ricketts SL, et.al. Plasticity of the neoplastic phenotype in vivo is regulated by epigenetic factors [J].Proc Natl Acad Sci U S A. 1998, 95(26):15333-8.
9: Maffini MV, Soto AM, Calabro JM, et.al. The stroma as a crucial target in rat mammary gland carcinogenesis [J].J Cell Sci. 2004, 117(Pt 8):1495-502.
相关评论：
1: Trosko JE. 'A failed paradigm: carcinogenesis is more than mutagenesis'.Mutagenesis. 1988 Jul;3(4):363-6.
2: Capp JP. Elements for an integrated approach to carcinogenesis.Bioessays. 2006 Feb;28(2):228.
3: Fahmy OG, Fahmy MJ. Gene elimination in carcinogenesis: reinterpretation of the somatic mutation theory. Cancer Res. 1970 Jan;30(1):195-205.
4: Cuthill S. Cellular epigenetics and the origin of cancer.Bioessays. 1994 Jun;16:393-4. Review.
最新进展：
1: Lin H, Yamada Y, Nguyen S, Linhart H, Jackson-Grusby L, Meissner A, Meletis K, Lo G, Jaenisch R. Suppression of intestinal neoplasia by deletion of Dnmt3b.Mol Cell Biol. 2006 Apr;26:2976-83.
2: Holm TM, Jackson-Grusby L, Brambrink T, Yamada Y, Rideout WM 3rd, Jaenisch R. Global loss of imprinting leads to widespread tumorigenesis in adult mice.Cancer Cell. 2005 Oct;8(4):275-85. Erratum in: Cancer Cell. 2005 Nov;8(5):433. Cancer Cell. 2006 Jan;9(1):69.
编辑：西门吹血
1: Jaffe LF. Epigenetic theories of cancer initiation [J]. Adv Cancer Res. 2003, 90:209-30.
2: Prehn RT. Cancers beget mutations versus mutations beget cancers [J]. Cancer Res. 1994, 54(20):5296-300.
肿瘤干细胞假说的历史回顾：
约150年前，病理学家Virchow等认为肿瘤来源于发育过程中某些潜伏的胚胎残余组织，这种推测基于对胚胎发育和某些肿瘤例如畸胎瘤的相似性的观察。1961年Bruce等发现只有1－4%的鼠类淋巴瘤细胞可以在被移植动物的脾脏形成克隆，1973年McCulloch等发现只有不到1%的髓白血病细胞可以在体外形成克隆。1977年Hamburger等发现1000－5000个实体瘤细胞中仅有1个细胞可以在软琼脂中形成细胞克隆。随着这些研究结果不断出现，上世纪70年代Potter和Pierce等分别提出肿瘤是干细胞分化成熟被抑制的结果。直到1997年Dick实验室分离到急性髓白血病干细胞，肿瘤干细胞的研究才逐渐升温，至今研究人员已经分别从慢性髓白血病、胶质瘤和乳腺癌中分离到具有特定免疫表型的肿瘤干细胞。
1: Jordan CT, Guzman ML.Mechanisms controlling pathogenesis and survival of leukemic stem cells [J].Oncogene. 2004, 23(43):7178-87.
2: Messner HA, McCulloch EA.Interacting cell populations affecting granulopoietic colony formation by normal and leukemic human marrow cells [J].Blood. 1973, 42(5):701-10.
3: Hamburger AW, Salmon SE. Primary bioassay of human tumor stem cells [J].Science. 1977, 197(4302):461-3.
4: Potter VR.Phenotypic diversity in experimental hepatomas: the concept of partially blocked ontogeny. The 10th Walter Hubert Lecture [J].Br J Cancer. 1978, 38(1):1-23.
5: Pierce GB.Relationship between differentiation and carcinogenesis [J]. J Toxicol Environ Health. 1977, 2:1335-42.
6: Bonnet D, Dick JE.Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell [J].Nat Med. 1997, 3(7):730-7.
癌症干细胞最新研究进展：
1: Reya T, Morrison SJ, Clarke MF, et.al. Stem cells, cancer, and cancer stem cells [J]. Nature. 2001, 414(6859):105-11.
2: Dalerba P, Cho RW, Clarke MF. Cancer Stem Cells: Models and Concepts.
Annu Rev Med. 2006 Sep 26;
3: Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL, Wahl GM. Cancer Stem Cells--Perspectives on Current Status and Future Directions: AACR Workshop on Cancer Stem Cells. Cancer Res. 2006 Oct 1;66(19):9339-44. Epub 2006 Sep 21.
癌症的表型遗传修饰改变假说历史回顾
早期研究人员发现化学诱癌实验产生的肿瘤，如果停止使用致癌剂和/或促癌剂，相当一部分肿瘤会通过重新分化而自发消失。上世纪40年代年Furth发现卵巢细胞移植到脾脏可以自发癌变。60年代King和McKinnell等将青蛙的肾癌细胞核转移到正常卵细胞中，发现这种卵细胞依然可以发育成正常的蝌蚪。70年代，Mintz和Illmensee等发现将畸胎瘤细胞移植至正常同系动物的胚泡内，结果产生不长肿瘤的嵌合型小鼠。Howell等发现肿瘤细胞和正常细胞的融合产生的细胞失去恶性表型。基于上述发现，1979年Holliday首先提出表型遗传修饰改变假说。80年代Sachs等将白血病细胞向同系动物的早期胚胎移植，发现白血病细胞可参与正常动物血液系统的发育，动物发育成熟后各系血液细胞均可发现白血病细胞的基因标记。90年代McCullough等将肝癌细胞向同系成年动物肝组织移植，发现癌细胞可参与正常肝脏细胞的更新；最近研究发现致癌剂作用于间质细胞却可以产生实质细胞肿瘤。
1: King TJ, DiBerardino MA.Transplantation of nuclei from the frog renal adenocarcinoma. I. Development of tumor nuclear-transplant embryos [J]. Ann N Y Acad Sci. 1965, 126(1):115-26.
2: McKinnell RG, Deggins BA, Labat DD.Transplantation of pluripotential nuclei from triploid frog tumors [J].Science. 1969, 165(891):394-6.
3: Mintz B, Illmensee K.Normal genetically mosaic mice produced from malignant teratocarcinoma cells [J].Proc Natl Acad Sci U S A. 1975, 72(9):3585-9.
4: Illmensee K, Mintz B.Totipotency and normal differentiation of single teratocarcinoma cells cloned by injection into blastocysts [J]. Proc Natl Acad Sci U S A. 1976, 73(2):549-53.
5: Howell AN, Sager R.Tumorigenicity and its suppression in cybrids of mouse and Chinese hamster cell lines [J]. Proc Natl Acad Sci U S A. 1978, 75(5):2358-62.
6: Holliday R.A new theory of carcinogenesis. Br J Cancer. 1979, 40(4):513-22.
7: Gootwine E, Webb CG, Sachs L.Participation of myeloid leukaemic cells injected into embryos in haematopoietic differentiation in adult mice [J]. Nature. 1982, 299(5878):63-5.
8: McCullough KD, Coleman WB, Ricketts SL, et.al. Plasticity of the neoplastic phenotype in vivo is regulated by epigenetic factors [J].Proc Natl Acad Sci U S A. 1998, 95(26):15333-8.
9: Maffini MV, Soto AM, Calabro JM, et.al. The stroma as a crucial target in rat mammary gland carcinogenesis [J].J Cell Sci. 2004, 117(Pt 8):1495-502.
相关评论：
1: Trosko JE. 'A failed paradigm: carcinogenesis is more than mutagenesis'.Mutagenesis. 1988 Jul;3(4):363-6.
2: Capp JP. Elements for an integrated approach to carcinogenesis.Bioessays. 2006 Feb;28(2):228.
3: Fahmy OG, Fahmy MJ. Gene elimination in carcinogenesis: reinterpretation of the somatic mutation theory. Cancer Res. 1970 Jan;30(1):195-205.
4: Cuthill S. Cellular epigenetics and the origin of cancer.Bioessays. 1994 Jun;16:393-4. Review.
最新进展：
1: Lin H, Yamada Y, Nguyen S, Linhart H, Jackson-Grusby L, Meissner A, Meletis K, Lo G, Jaenisch R. Suppression of intestinal neoplasia by deletion of Dnmt3b.Mol Cell Biol. 2006 Apr;26:2976-83.
2: Holm TM, Jackson-Grusby L, Brambrink T, Yamada Y, Rideout WM 3rd, Jaenisch R. Global loss of imprinting leads to widespread tumorigenesis in adult mice.Cancer Cell. 2005 Oct;8(4):275-85. Erratum in: Cancer Cell. 2005 Nov;8(5):433. Cancer Cell. 2006 Jan;9(1):69.
编辑：西门吹血
作者: cypress1975
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