细胞分裂和癌变机制新假说
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摘要
细胞为何分裂,癌症如何发生,至今仍众说纷纭。本文通过分析细胞为什么会分裂,提出了关于细胞分裂和癌变新假说:细胞内渗透压缓慢升高推动细胞体积不断增大直至细胞膜无法支撑而"破裂",这样周而复始的循环是细胞为什么会不断分裂的根本原因。癌变是由于肿瘤细胞内渗透压升高速度明显快于其起源正常细胞结果,所以肿瘤细胞更容易"破裂",也就是分裂速度加快。最后,本文认为调节细胞内渗透压的方法可以应用于恶性肿瘤的治疗。由于肿瘤细胞渗透压增速并更容易"破裂",因此,突然进一步升高肿瘤细胞内渗透压,可能导致肿瘤细胞"胀亡",从而达到治疗的目的。
Presently, there are still many controversies about the mechanism of cell division and carcinogenesis.Here, through exploring the question why cells can divide, the author presents a new hypothesis about cell division and carcinogenesis: slowly increased osmotic pressure within cells continually enlarges the cell volume until the tolerance limit of cell membranes to "split", and such a cycle is the real cause of the continual cell division. Carcinogensis primarily results from the faster increase of osmotic pressure within cancer cells compared with that of the origin normal cells. Therefore, cancer cells get easier "rupture" or faster division. Based on the hypothesis, the author puts forward that the methods of regulating osmotic pressure within cells may be used to treat malignancies. Due to the faster increase of osmotic pressure and easier"rupture" of cancer cells, suddenly further increasing the osmotic pressure within cancer cells may kill them by oncosis.
Presently, there are still many controversies about the mechanism of cell division and carcinogenesis.Here, through exploring the question why cells can divide, the author presents a new hypothesis about cell division and carcinogenesis: slowly increased osmotic pressure within cells continually enlarges the cell volume until the tolerance limit of cell membranes to "split", and such a cycle is the real cause of the continual cell division. Carcinogensis primarily results from the faster increase of osmotic pressure within cancer cells compared with that of the origin normal cells. Therefore, cancer cells get easier "rupture" or faster division. Based on the hypothesis, the author puts forward that the methods of regulating osmotic pressure within cells may be used to treat malignancies. Due to the faster increase of osmotic pressure and easier"rupture" of cancer cells, suddenly further increasing the osmotic pressure within cancer cells may kill them by oncosis.
引文
[1]Vogelstein B, Papadopoulos N, Velculescu VE, et al. Cancer genome landscapes[J]. Science, 2013, 339(6127):1546-1558.
[2]Dagogo-Jack I, Shaw AT. Tumour heterogeneity and resistance to cancer therapies[J]. Nat Rev Clin Oncol, 2018,15(2):81-94.
[3]Hanahan D, Weinberg RA. Hallmarks of cancer:the next generation[J]. Cell, 2011, 144(5):646-674.
[4]Hartwell LH, Weinert TA. Checkpoints:controls that ensure the order of cell cycle events[J]. Science, 1989,246(4930):629-634.
[5]Nurse P. A long twentieth century of the cell cycle and beyond[J]. Cell, 2000, 100(1):71-78.
[6]Hoffmann EK1, Pedersen SF. Cell volume homeostatic mechanisms:effectors and signalling pathways[J]. Acta Physiol(Oxf), 2011, 202(3):465-485.
[7]Ullrich N, Sontheimer H. Cell cycle-dependent expression of a glioma-specific chloride current:proposed link to cytoskeletal changes[J]. Am J Physiol, 1997, 273(4 Pt 1):C1290-1297.
[8]G?nczi M, Szentandrássy N, Fül?p L, et al. Hypotonic stress influence the membrane potential and alter the proliferation of keratinocytes in vitro[J]. Exp Dermatol, 2007, 16(4):302-310.
[9]Dascalu A, Matithyou A, Oron Y, et al. A hyperosmotic stimulus elevates intracellular calcium and inhibits proliferation of a human keratinocyte cell line[J]. J Invest Dermatol, 2000, 115(4):714-718.
[10]Cone CD Jr, Cone CM. Induction of mitosis in mature neuronsincentralnervoussystembysustained depolarization[J]. Science, 1976, 192(4235):155-158.
[11]Duesberg P, Fabarius A, Hehlmann R. Aneuploidy, the primary cause of the multilateral genomic instability of neoplastic and preneoplastic cells[J]. IUBMB Life, 2004,56(2):65-81.
[12]Cone CD Jr. Unified theory on the basic mechanism of normal mitotic control and oncogenesis[J]. J Theor Biol,1971, 30(1):151-181.
[13]Lambert IH, Hoffmann EK, Pedersen SF. Cell volume regulation:physiology and pathophysiology[J]. Acta Physiol(Oxf), 2008, 194(4):255-282.
[14]Calderón-Monta?o JM, Burgos-Morón E, Orta ML, et al.Evaluating the cancer therapeutic potential of cardiac glycosides[J]. Biomed Res Int, 2014, 2014(12):794930.
[15]Shiozaki A, Ichikawa D, Kosuga T, et al. Regulation of osmolality for cancer treatment[J]. J Physiol Sci, 2017,67(3):353-360.
[16]Mijatovic T, Dufrasne F, Kiss R. Na+/K+-ATPase and cancer[J]. Pharm Pat Anal, 2012, 1(1):91-106.
[2]Dagogo-Jack I, Shaw AT. Tumour heterogeneity and resistance to cancer therapies[J]. Nat Rev Clin Oncol, 2018,15(2):81-94.
[3]Hanahan D, Weinberg RA. Hallmarks of cancer:the next generation[J]. Cell, 2011, 144(5):646-674.
[4]Hartwell LH, Weinert TA. Checkpoints:controls that ensure the order of cell cycle events[J]. Science, 1989,246(4930):629-634.
[5]Nurse P. A long twentieth century of the cell cycle and beyond[J]. Cell, 2000, 100(1):71-78.
[6]Hoffmann EK1, Pedersen SF. Cell volume homeostatic mechanisms:effectors and signalling pathways[J]. Acta Physiol(Oxf), 2011, 202(3):465-485.
[7]Ullrich N, Sontheimer H. Cell cycle-dependent expression of a glioma-specific chloride current:proposed link to cytoskeletal changes[J]. Am J Physiol, 1997, 273(4 Pt 1):C1290-1297.
[8]G?nczi M, Szentandrássy N, Fül?p L, et al. Hypotonic stress influence the membrane potential and alter the proliferation of keratinocytes in vitro[J]. Exp Dermatol, 2007, 16(4):302-310.
[9]Dascalu A, Matithyou A, Oron Y, et al. A hyperosmotic stimulus elevates intracellular calcium and inhibits proliferation of a human keratinocyte cell line[J]. J Invest Dermatol, 2000, 115(4):714-718.
[10]Cone CD Jr, Cone CM. Induction of mitosis in mature neuronsincentralnervoussystembysustained depolarization[J]. Science, 1976, 192(4235):155-158.
[11]Duesberg P, Fabarius A, Hehlmann R. Aneuploidy, the primary cause of the multilateral genomic instability of neoplastic and preneoplastic cells[J]. IUBMB Life, 2004,56(2):65-81.
[12]Cone CD Jr. Unified theory on the basic mechanism of normal mitotic control and oncogenesis[J]. J Theor Biol,1971, 30(1):151-181.
[13]Lambert IH, Hoffmann EK, Pedersen SF. Cell volume regulation:physiology and pathophysiology[J]. Acta Physiol(Oxf), 2008, 194(4):255-282.
[14]Calderón-Monta?o JM, Burgos-Morón E, Orta ML, et al.Evaluating the cancer therapeutic potential of cardiac glycosides[J]. Biomed Res Int, 2014, 2014(12):794930.
[15]Shiozaki A, Ichikawa D, Kosuga T, et al. Regulation of osmolality for cancer treatment[J]. J Physiol Sci, 2017,67(3):353-360.
[16]Mijatovic T, Dufrasne F, Kiss R. Na+/K+-ATPase and cancer[J]. Pharm Pat Anal, 2012, 1(1):91-106.