Welcome To The Cancer Environment

The organism can only be understood in its environments, and a cell can’t be understood without reference to the tissue and organism in which it lives.’ Ray Peat PhD

When you listen to what the medical “experts” say about cancer, you might come away with the impression that there has been complete agreement – in the vast amounts of scientific literature on the subject – regarding the nature of the disease and, as such, the kinds of treatments worthy of consideration.

Even though that impression is not accurate, few people are aware that there is a long history of research and experimentation questioning the validity of the standard paradigm – which views cancer as a genetically driven disease of the cell – opening up the possibility for alternative forms of treatment.

‘The somatic mutation theory of carcinogenesis has been the dominant force driving cancer research during the 20th century. In brief, it proposes that successive DNA mutations in a single cell cause cancer…’ (C Sonnenschein, A M Soto. 2000)

‘…its…continuous invocation of ‘programs’ and ‘mechanisms’ is a reflection of inadequate metaphors borrowed respectively from computer sciences and outdated physics; organisms are neither computers nor machines.’ (Carlos Sonnenschein, Ana M Soto, 2013)

The idea, however, that cancer is not a random genetic event – but a systemic disease that can result from a wide variety of metabolic stressors – has faced significant resistance in both the scientific and medical communities, regardless of the quality of the evidence supporting it.

‘We argue that it is necessary to abandon the somatic mutation theory…We propose the adoption of an alternative theory, the tissue organization field theory of carcinogenesis…’ (C Sonnenschein, A M Soto. 2000)

‘…the tissue organization field theory…incorporates the premise that proliferation and motility are the default state of all cells, and that carcinogenesis is due to alterations on the reciprocal interactions among cells and between cells and their extracellular matrix…There are multiple examples of normalization of cells that once belonged to a cancer…’ (Carlos Sonnenschein, Ana M Soto, 2013)

The pushback to this theory arises because it threatens the status quo, suggesting that cancer prevention and treatment need not focus on discovering “responsible” genes and seeking out and destroying “guilty” cells. Moreover, it implies that the dominant approach may be more harmful than helpful.

‘In the important realm of experimental cancer research, the proposed change would mean a switch from a subcellular, gene-centric approach to a tissue-based organicist one, in which a combined top-down and bottom-up strategy would include systems biology components.’ (Carlos Sonnenschein and Ana M. Soto, 2011)

‘The regulatory power of a mass of contiguous normal cells is expressed in its capacity to normalize the appearance and growth behavior of solitary homophilic neoplastic cells…’ (Harry Rubin, 2006)

Destroying or removing “cancer cells” in the currently accepted way – surgery, chemotherapy and radiation – has been shown to have potentially dangerous repercussions by increasing the cancer-promoting capability of surrounding tissue environments.

‘Put another way, cancer results from a breakdown of tissue organization that disrupts the normal inhibitions of proliferation that are inherent in the tissue architecture of a multicellular society of cells.’ (C. Sonnenschein, et al., 1999)

Alternatively, it makes sense that any approach which can effectively improve tissue environments is likely to have the opposite effect, preventing or perhaps even reversing the spread of cancer.

‘One of the predictions of the tissue organization field theory is that carcinogenesis can potentially be reversed… Experimentally, the reversal of neoplastic behavior has been accomplished repeatedly when neoplastic cells were placed within the normal tissues from which they originated.’ (Maricel V Maffini, et al., 2005)

‘Normal growth behavior is reintroduced in solitary, carcinogen-initiated epidermal cells by contact with an excess of normal epidermal cells.” (Harry Rubin, 2007)

And the worsening of tissue microenvironments influences the likelihood that tumours will spread or metastasize. It is a circumstance that is overwhelmingly responsible for cancer mortality.

‘Metastases are defined as secondary tumors that develop at a distance from their primary originators; they are the cause of death for 90% of cancer patients…the prevailing consensus is that metastases are not explained accurately, and, more importantly, they are far from being successfully managed.’ ( Carlos Sonnenschein, Ana M Soto, 2015)

‘…behavior of normal cells is ordered by their topological relations in tissues and other homeostatic influences of the organism. Weakening of these ordering relations may contribute to malignant transformation…’ (H Rubin, 1990)

‘…cancer metastases, as their primary cancers, are not cell-based events but represent, instead, tissue-based phenomena.’ ( Carlos Sonnenschein, Ana M Soto, 2013)

Rather than random genetic mutations driving the creation of “cancer cells”, based on good quality evidence, it makes sense to see biological stress as the central factor in the development of an internal cancer environment.

Continuous stress interfering with metabolic energy – or exceeding the amount required to cope with stress – can be one general way of understanding how the conditions come about that change the tissue, damage the cells (as well as DNA), and encourage cancer.

‘We challenge the notion that cancer is a cellular problem caused by mutated genes by assessing…an alternative view that regards carcinogenesis as a developmental process gone awry.’ (Ana M Soto, Carlos Sonnenschein, 2005)

‘…interactions among different components of a tissue cannot be reduced to cellular events…carcinogenesis takes place at the tissue level of biological organization……while normal cells already carry mutations, they do not end up becoming cancer cells…From this perspective, these mutations would be irrelevant as suggested by the repeated instances where cells from diverse cancer types were normalized when placed within a normal field.’ ( Ana M Soto, Carlos Sonnenschein, 2011)

The stress substances – including cortisol, serotonin, endotoxin, nitric oxide, estrogen, lactate, and other inflammatory and fibrotic things – often increase side by side with aging. And they, directly and indirectly, impact the ability of tissue environments to protect against (or reverse) the cancer behaviour of the cell.

‘…damage accumulates with age, as does an increasingly permissive local environment for tumor growth…The order that controls heterogeneity is weakened with age and contributes to the origin and progression of disordered growth.’ (H Rubin, 1999)

‘…findings reveal unanticipated communication between stress-induced neural signalling and inflammation, which regulates tumour lymphatic architecture and lymphogenous tumour cell dissemination.’ (Caroline P. Le, et al., 2016)

Increased circulation of bacterial endotoxin (LPS or lipopolysaccharide) is one thing that is known to promote inflammatory conditions, which can induce cancer development and metastasis.

‘Inflammation has been known to be linked to invasion or metastasis of breast cancer, which has poor prognosis…Here we show that T-LAK cell-originated protein kinase (TOPK) mediates pro-inflammatory endotoxin lipopolysaccharide (LPS)-induced breast cancer cell migration and invasion.’  (Min-Ah Seol, et al., 2017)

‘NF-kappaB is one of the key factors connecting inflammation with cancer progression…LPS increased the invasive ability of pancreatic cancer cells, while blockade of NF-kappaB pathway decreased the LPS-dependent increased invasive ability…’ (Mio Ikebe, et al., 2009)

‘Our findings suggest that inhibiting LPS-induced TLR4 signaling could improve therapeutic outcomes by preventing cancer metastasis during the perioperative period of CRC (colorectal cancer) resection.’ (Rich Y C Hsu, et al., 2011)

Polyunsaturated fats (PUFAs) get stored in (and released from) the tissue. And they are a fundamental and powerful driver of inflammation and the growth and spread of cancer.

‘Arachidonic acid (ARA) is metabolized by cyclooxygenase (COX) and cytochrome P450 to produce proangiogenic metabolites. Specifically, epoxyeicosatrienoic acids (EETs) produced from the P450 pathway…promote angiogenesis, tumor growth, and metastasis.’ (Amy A Rand, et al., 2017)

‘…dietary fat promotes the growth of initiated cells, thus contributing to the higher risk of many human cancers…high-fat diets containing corn oil, soybean oil or safflower oil, which are 55–80% linoleic acid, increase the rate of growth of established tumors…’ (Ivan Rusyn, et al., 1999)

‘…we find that neutrophil-derived leukotrienes [metabolites of arachidonic acid] aid the colonization of distant tissue by selectively expanding the sub-pool of cancer cells that retain high tumorigenic potential.’ (Stefanie K Wculek, Ilaria Malanchi, 2015)

Endotoxin and PUFAs promote nitric oxide (NO), and NO is another potent mediator of inflammation, which plays a role in developing a tissue environment that is increasingly capable of promoting cancer initiation and progression.

‘…these data suggest that, in head and neck cancer, the increased NOS activity can be regarded as a novel biologic marker for tumor progression related to angiogenesis…’ (Oreste Gallo, et al., 1999)

‘Inducible nitric oxide synthase (iNOS) is associated with poor survival in patients with breast cancer by increasing tumor aggressiveness…targeted therapy with iNOS inhibitors is able to inhibit not only tumor cell proliferation…self-renewal and migration, reducing tumor growth, tumor initiation, and the number of lung metastases.’ (Sergio Granados-Principal, et al., 2015)

‘…role for NO production from iNOS in human lung cancer because high concentrations of this short molecule may transform to highly reactive compounds such as peroxynitrite; moreover, through the upregulator NF-kB, they can induce a chronic inflammatory state representing an elevated risk for cell transformation to cancer.’ (Speranza L, et al., 2007)

Exposure to chronic or acute stress wastes blood sugar reserves. In addition, it leads to increased release of stress substances (including bacterial endotoxin) and a rise in systemic levels of polyunsaturated free fatty acids.

The combination of many of the above factors can be a significant determinant of the stress conditions that promote tissue damage, genetic changes, blood sugar dysregulation, and the irregular cell activity of cancer and related metabolic illnesses.

‘…chronic periods of stress can be detrimental to health by increasing inflammation and promoting the progression of diseases including cancer…we show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape.’ (Caroline P. Le, et al., 2016)

‘Our findings provide a hitherto-undescribed direct role of increased aerobic glycolysis in inducing the cancer phenotype, in which increased glycolytic activity regulates the canonical oncogenic pathways…additional evidence for how hyperglycemia in diseases such as obesity and diabetes could provide a microenvironment that results in higher risk of some cancers.’ (Yasuhito Onodera, et al., 2013)

Estrogen levels are known to rise due to ongoing exposure to inflammatory stress substances, potentially causing genetic changes and cancer development. Estrogen blood tests do not account for the amount of estrogen trapped in tissue that causes the most harm.

‘…findings suggest that exposure to estrogen…is capable of driving genomic instability, a well-defined early event in breast cancer development. Given that estrogen levels in normal/benign breast tissue are known to be 6-7 times that of circulating estrogen levels, our findings suggest a mechanism through which BRCA1 carriers, through enhanced production of DNA damaging estrogen metabolites, may acquire the genetic alterations that initiate neoplastic transformation in breast tissue…Similarly, levels of estrogen in ovarian tissues greatly exceed that of circulating estrogen, suggesting that this model may also explain the substantially increased risk of ovarian cancer in BRCA1 carriers…’ (Kienan I Savage, et al., 2014)

‘The knowledge that breast cancer in women is associated with prolonged exposure to high levels of estrogens gives relevance to this model of estrogen induced carcinogenesis…’ ( J Russo, Irma H Russo, 2006) 

Avoiding consumption of the PUFAs and eating high-quality protein – from milk, cheese and gelatinous cuts of meat – and simple and easy-to-digest sugars – from sweet ripe fruit, fruit juice, white sugar and honey – is a potentially powerful approach to suppressing stress. It helps regulate blood sugar and lower exposure to dangerous fats (ingested and stored in tissue). It is also a logical way to improve tissue organization, redirecting cellular behaviour away from cancer progression.

‘…these observations may lead to a new paradigm for control and treatment of cancer in situ…it may be possible to redirect tumorigenic cells to normal cell function by exposure to substances present within normal tissues.’ (Karen M Bussard, et al., 2010)

‘This provides a mechanism through which interaction with the normal mammary microenvironment may suppress tumorigenesis…the normal microenvironment redirects…tumorigenic cells to participate in the regeneration of a normal, functional mammary gland.’ (B W Booth, et al., 2010)

Some other things that protect include increasing carbon dioxide levels (with bag breathing or adaptation to higher altitudes, for example), exposure to daylight, therapeutic use of red light and pregnenolone and progesterone supplementation. And vitamins E and A, caffeine, glycine, aspirin, and the antihistamine cyproheptadine.

Alternatively, things that lower stress and allow thyroid metabolism to function more effectively (including the therapeutic use of white sugar) are likely to be very helpful.

‘A deeper understanding of the role(s) of tissue and tumor microenvironments in the pathogenesis of cancer is essential to design more effective strategies for the management of this disease.’ (Ezio Laconi, et al., 2008)

‘…if a cancer cell exists as a discrete entity distinguishable from a normal cell, it has certainly been very uncooperative in revealing what it has ‘invented’ to deserve the fame it has acquired. More to the point, cells isolated from cancers revert to normalcy when placed in a normal microenvironment.’ ( Carlos Sonnenschein, Ana M Soto, 2013)

Copyright 2021, by Dan M @ CowsEatGrass. All rights reserved (except for quotations and images having their own protected copyrights). This copyright protects author-publisher Dan M’s right to future publication of his work in any manner, in any and all media — utilizing technology now known or hereafter devised — throughout the world in perpetuity. Everything described in this publication is for information purposes only. The author-publisher, Dan M, is not directly or indirectly presenting or recommending any part of this publication’s data as a diagnosis or prescription for any ailment of any reader. If anyone uses this information without the advice of their professional health adviser, they are prescribing for themselves, and the author- publisher assumes no responsibility or liability. Persons using any of this data do so at their own risk and must take personal responsibility for what they don’t know as well as for what they do know.

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Bartsch H, Nair J, Owen RW. Dietary polyunsaturated fatty acids and cancers of the breast and colorectum: emerging evidence for their role as risk modifiers. Carcinogenesis. 1999 Dec;20(12):2209-18.

Booth BW, Boulanger CA, Anderson LH, Smith GH. The normal mammary microenvironment suppresses the tumorigenic phenotype of mouse mammary tumor virus-neu-transformed mammary tumor cells. Oncogene. 2011 Feb 10;30(6):679-89.

Bussard KM, Boulanger CA, Booth BW, Bruno RD, Smith GH. Reprogramming human cancer cells in the mouse mammary gland. Cancer Res. 2010 Aug 1;70(15):6336-43. 

Chamras H, Barsky SH, Ardashian A, Navasartian D, Heber D, Glaspy JA. Novel interactions of vitamin E and estrogen in breast cancer. Nutr Cancer. 2005;52(1):43-8.

Changou CA, Chen YR, Xing L, Yen Y, Chuang FY, Cheng RH, Bold RJ, Ann DK, Kung HJ. Arginine starvation-associated atypical cellular death involves mitochondrial dysfunction, nuclear DNA leakage, and chromatin autophagy. Proc Natl Acad Sci U S A. 2014 Sep 30;111(39):14147-52.

Chen C, Khismatullin DB. Lipopolysaccharide induces the interactions of breast cancer and endothelial cells via activated monocytes. Cancer Lett. 2014 Apr 1;345(1):75-84.

Chowdhury AR, Long A, Fuchs SY, Rustgi A, Avadhani NG. Mitochondrial stress-induced p53 attenuates HIF-1α activity by physical association and enhanced ubiquitination. Oncogene. 2017 Jan 19;36(3):397-409.

Dong J, Cheng M, Sun H. Function of inducible nitric oxide synthase in the regulation of cervical cancer cell proliferation and the expression of vascular endothelial growth factor. Mol Med Rep. 2014 Feb;9(2):583-9.

Gallo O, Masini E, Morbidelli L, Franchi A, Fini-Storchi I, Vergari WA, Ziche M. Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer. J Natl Cancer Inst. 1998 Apr 15;90(8):587-96.

Ghosh J, Myers CE. Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13182-7. 

Granados-Principal S, Liu Y, Guevara ML, Blanco E, Choi DS, Qian W, Patel T, Rodriguez AA, Cusimano J, Weiss HL, Zhao H, Landis MD, Dave B, Gross SS, Chang JC. Inhibition of iNOS as a novel effective targeted therapy against triple-negative breast cancer. Breast Cancer Res. 2015 Feb 22;17(1):25.

Heber D. Prostate enlargement: the canary in the coal mine? Am J Clin Nutr. 2002 Apr;75(4):605-6.

Hendrix MJ, Seftor EA, Seftor RE, Kasemeier-Kulesa J, Kulesa PM, Postovit LM. Reprogramming metastatic tumour cells with embryonic microenvironments. Nat Rev Cancer. 2007 Apr;7(4):246-55.

Hirschhaeuser F, Sattler UG, Mueller-Klieser W. Lactate: a metabolic key player in cancer. Cancer Res. 2011 Nov 15;71(22):6921-5.

Holtzman S. Retinyl acetate inhibits estrogen-induced mammary carcinogenesis in female ACI rats. Carcinogenesis. 1988 Feb;9(2):305-7.

Hsu RY, Chan CH, Spicer JD, Rousseau MC, Giannias B, Rousseau S, Ferri LE. LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis. Cancer Res. 2011 Mar 1;71(5):1989-98.

Ikebe M, Kitaura Y, Nakamura M, Tanaka H, Yamasaki A, Nagai S, Wada J, Yanai K, Koga K, Sato N, Kubo M, Tanaka M, Onishi H, Katano M. Lipopolysaccharide (LPS) increases the invasive ability of pancreatic cancer cells through the TLR4/MyD88 signaling pathway. J Surg Oncol. 2009 Dec 15;100(8):725-31.

Key TJ, Appleby PN, Reeves GK, Travis RC, Brinton LA, Helzlsouer KJ, Dorgan JF, Gapstur SM, Gaudet MM, Kaaks R, Riboli E, Rinaldi S, Manjer J, Hallmans G, Giles GG, Le Marchand L, Kolonel LN, Henderson BE, Tworoger SS, Hankinson SE, Zeleniuch-Jacquotte A, Koenig K, Krogh V, Sieri S, Muti P, Ziegler RG, Schairer C, Fuhrman BJ, Barrett-Connor E, Laughlin GA, Grant EJ, Cologne J, Ohishi W, Hida A, Cauley JA, Fourkala EO, Menon U, Rohan TE, Strickler HD, Gunter MJ; Endogenous Hormones and Breast Cancer Collaborative Group. Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies. Steroids. 2015 Jul;99(Pt A):49-55.

Koo J, Cabarcas-Petroski S, Petrie JL, Diette N, White RJ, Schramm L. Induction of proto-oncogene BRF2 in breast cancer cells by the dietary soybean isoflavone daidzein. BMC Cancer. 2015 Nov 16;15:905.

Kothapalli KS, Ye K, Gadgil MS, Carlson SE, O’Brien KO, Zhang JY, Park HG, Ojukwu K, Zou J, Hyon SS, Joshi KS, Gu Z, Keinan A, Brenna JT. Positive Selection on a Regulatory Insertion-Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid. Mol Biol Evol. 2016 Jul;33(7):1726-39.

Labrie F, Luu-The V, Bélanger A, Lin SX, Simard J, Pelletier G, Labrie C. Is dehydroepiandrosterone a hormone? J Endocrinol. 2005 Nov;187(2):169-96.

Laconi E, Doratiotto S, Vineis P. The microenvironments of multistage carcinogenesis. Semin Cancer Biol. 2008 Oct;18(5):322-9.

Launay JM, Birraux G, Bondoux D, Callebert J, Choi DS, Loric S, Maroteaux L. Ras involvement in signal transduction by the serotonin 5-HT2B receptor. J Biol Chem. 1996 Feb 9;271(6):3141-7.

Le CP, Nowell CJ, Kim-Fuchs C, Botteri E, Hiller JG, Ismail H, Pimentel MA, Chai MG, Karnezis T, Rotmensz N, Renne G, Gandini S, Pouton CW, Ferrari D, Möller A, Stacker SA, Sloan EK. Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination. Nat Commun. 2016 Mar 1;7:10634.

Maffini MV, Calabro JM, Soto AM, Sonnenschein C. Stromal regulation of neoplastic development: age-dependent normalization of neoplastic mammary cells by mammary stroma. Am J Pathol. 2005 Nov;167(5):1405-10.

Maity G, De A, Das A, Banerjee S, Sarkar S, Banerjee SK. Aspirin blocks growth of breast tumor cells and tumor-initiating cells and induces reprogramming factors of mesenchymal to epithelial transition. Lab Invest. 2015 Jul;95(7):702-17.

Mohammed H, Russell IA, Stark R, Rueda OM, Hickey TE, Tarulli GA, Serandour AA, Birrell SN, Bruna A, Saadi A, Menon S, Hadfield J, Pugh M, Raj GV, Brown GD, D’Santos C, Robinson JL, Silva G, Launchbury R, Perou CM, Stingl J, Caldas C, Tilley WD, Carroll JS. Progesterone receptor modulates ERα action in breast cancer. Nature. 2015 Jul 16;523(7560):313-7.

Nakagawa H, Ueda T, Ito S, Shiraishi T, Taniguchi H, Kayukawa N, Nakanishi H, Ushijima S, Kanazawa M, Nakamura T, Naya Y, Hongo F, Kamoi K, Okihara K, Ukimura O. Androgen suppresses testicular cancer cell growth in vitro and in vivo. Oncotarget. 2016 Jun 7;7(23):35224-32.

Onodera Y, Nam JM, Bissell MJ. Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways. J Clin Invest. 2014 Jan;124(1):367-84.

Padickakudy R, Pereyra D, Offensperger F, Jonas P, Oehlberger L, Schwarz C, Haegele S, Assinger A, Brostjan C, Gruenberger T, Starlinger P. Bivalent role of intra-platelet serotonin in liver regeneration and tumor recurrence in humans. J Hepatol. 2017 Dec;67(6):1243-1252.

Palmer S, Albergante L, Blackburn CC, Newman TJ. Thymic involution and rising disease incidence with age. Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):1883-1888.

Park GS, Kim JH. LPS Up-Regulates ICAM-1 Expression in Breast Cancer Cells by Stimulating a MyD88-BLT2-ERK-Linked Cascade, Which Promotes Adhesion to Monocytes. Mol Cells. 2015 Sep;38(9):821-8.

Patil PU, D’Ambrosio J, Inge LJ, Mason RW, Rajasekaran AK. Carcinoma cells induce lumen filling and EMT in epithelial cells through soluble E-cadherin-mediated activation of EGFR. J Cell Sci. 2015 Dec 1;128(23):4366-79.

Peskin BS, Carter MJ. Chronic cellular hypoxia as the prime cause of cancer: what is the de-oxygenating role of adulterated and improper ratios of polyunsaturated fatty acids when incorporated into cell membranes? Med Hypotheses. 2008;70(2):298-304.

Plonk JW, Bivens CH, Feldman JM. Inhibition of hypoglycemia-induced cortisol secretion by the serotonin antagonist cyproheptadine. J Clin Endocrinol Metab. 1974 May;38(5):836-40.

Rand AA, Barnych B, Morisseau C, Cajka T, Lee KSS, Panigrahy D, Hammock BD. Cyclooxygenase-derived proangiogenic metabolites of epoxyeicosatrienoic acids. Proc Natl Acad Sci U S A. 2017 Apr 25;114(17):4370-4375.

Romero L, Muñoz C, López A, Vilches J. Relación de la prolactina con la hiperplasia nodular y el carcinoma de próstata [Relation of prolactin with nodular hyperplasia and carcinoma of the prostate]. Actas Urol Esp. 1991 Nov-Dec;15(6):503-9. Spanish.

Rose DP, Connolly JM. Effects of fatty acids and eicosanoid synthesis inhibitors on the growth of two human prostate cancer cell lines. Prostate. 1991;18(3):243-54.

Rosendahl AH, Perks CM, Zeng L, Markkula A, Simonsson M, Rose C, Ingvar C, Holly JM, Jernström H. Caffeine and Caffeic Acid Inhibit Growth and Modify Estrogen Receptor and Insulin-like Growth Factor I Receptor Levels in Human Breast Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1877-87.

Rubin H. Cell damage, aging and transformation: a multilevel analysis of carcinogenesis. Anticancer Res. 1999 Nov-Dec;19(6A):4877-86.

Rubin H. Ordered heterogeneity and its decline in cancer and aging. Adv Cancer Res. 2007;98:117-47.

Rubin H. Rethinking “cancer as a dynamic developmental disorder” a quarter century later. Cancer Res. 2009 Mar 15;69(6):2171-5.

Rubin H. The significance of biological heterogeneity. Cancer Metastasis Rev. 1990 Jul;9(1):1-20.

Rubin H. What keeps cells in tissues behaving normally in the face of myriad mutations? Bioessays. 2006 May;28(5):515-24.

Russo J, Russo IH. The role of estrogen in the initiation of breast cancer. J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):89-96.

Rusyn I, Bradham CA, Cohn L, Schoonhoven R, Swenberg JA, Brenner DA, Thurman RG. Corn oil rapidly activates nuclear factor-kappaB in hepatic Kupffer cells by oxidant-dependent mechanisms. Carcinogenesis. 1999 Nov;20(11):2095-100.

Samudio I, Harmancey R, Fiegl M, Kantarjian H, Konopleva M, Korchin B, Kaluarachchi K, Bornmann W, Duvvuri S, Taegtmeyer H, Andreeff M. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest. 2010 Jan;120(1):142-56.

San-Millán I, Brooks GA. Reexamining cancer metabolism: lactate production for carcinogenesis could be the purpose and explanation of the Warburg Effect. Carcinogenesis. 2017 Feb 1;38(2):119-133.

Santner SJ, Santen RJ. Inhibition of estrone sulfatase and 17 beta-hydroxysteroid dehydrogenase by antiestrogens. J Steroid Biochem Mol Biol. 1993 May;45(5):383-90. 

Savage KI, Matchett KB, Barros EM, Cooper KM, Irwin GW, Gorski JJ, Orr KS, Vohhodina J, Kavanagh JN, Madden AF, Powell A, Manti L, McDade SS, Park BH, Prise KM, McIntosh SA, Salto-Tellez M, Richard DJ, Elliott CT, Harkin DP. BRCA1 deficiency exacerbates estrogen-induced DNA damage and genomic instability. Cancer Res. 2014 May 15;74(10):2773-2784.

Seol MA, Park JH, Jeong JH, Lyu J, Han SY, Oh SM. Role of TOPK in lipopolysaccharide-induced breast cancer cell migration and invasion. Oncotarget. 2017 Jun 20;8(25):40190-40203.

Slebe F, Rojo F, Vinaixa M, García-Rocha M, Testoni G, Guiu M, Planet E, Samino S, Arenas EJ, Beltran A, Rovira A, Lluch A, Salvatella X, Yanes O, Albanell J, Guinovart JJ, Gomis RR. FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth. Nat Commun. 2016 Apr 5;7:11199.

Sonnenschein C, Soto AM. Cancer Metastases: So Close and So Far. J Natl Cancer Inst. 2015 Aug 17;107(11):djv236.

Sonnenschein C, Soto AM. Somatic mutation theory of carcinogenesis: why it should be dropped and replaced. Mol Carcinog. 2000 Dec;29(4):205-11.

Sonnenschein C, Soto AM. The aging of the 2000 and 2011 Hallmarks of Cancer reviews: a critique. J Biosci. 2013 Sep;38(3):651-63.

Sonnenschein C, Soto AM. The death of the cancer cell. Cancer Res. 2011 Jul 1;71(13):4334-7.

C. Sonnenschein, A. M. Soto. E. J. Roemer. E. J. Roemer. The Society of Cells: Cancer and control of cell proliferation. N Engl J Med 1999; 341:63-64.

Soto AM, Sonnenschein C. Emergentism as a default: cancer as a problem of tissue organization. J Biosci. 2005 Feb;30(1):103-18.

Soto AM, Sonnenschein C. The tissue organization field theory of cancer: a testable replacement for the somatic mutation theory. Bioessays. 2011 May;33(5):332-40.

Speranza L, De Lutiis MA, Shaik YB, Felaco M, Patruno A, Tetè S, Tetè A, Mastrangelo F, Madhappan B, Castellani ML, Conti F, Vecchiet J, Theoharides TC, Conti P, Grilli A. Localization and activity of iNOS in normal human lung tissue and lung cancer tissue. Int J Biol Markers. 2007 Jul-Sep;22(3):226-31. Erratum in: Int J Biol Markers. 2007 Oct-Dec;22(4):312. Tetè, A [corrected to Tetè, S].

Takemoto Y, Ito A, Niwa H, Okamura M, Fujiwara T, Hirano T, Handa N, Umehara T, Sonoda T, Ogawa K, Tariq M, Nishino N, Dan S, Kagechika H, Yamori T, Yokoyama S, Yoshida M. Identification of Cyproheptadine as an Inhibitor of SET Domain Containing Lysine Methyltransferase 7/9 (Set7/9) That Regulates Estrogen-Dependent Transcription. J Med Chem. 2016 Apr 28;59(8):3650-60.

Tao M, Liu L, Shen M, Zhi Q, Gong FR, Zhou BP, Wu Y, Liu H, Chen K, Shen B, Wu MY, Shou LM, Li W. Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac. Cell Cycle. 2016;15(3):381-93.

Thienpont B, Steinbacher J, Zhao H, D’Anna F, Kuchnio A, Ploumakis A, Ghesquière B, Van Dyck L, Boeckx B, Schoonjans L, Hermans E, Amant F, Kristensen VN, Peng Koh K, Mazzone M, Coleman M, Carell T, Carmeliet P, Lambrechts D. Tumour hypoxia causes DNA hypermethylation by reducing TET activity. Nature. 2016 Sep 1;537(7618):63-68.

Wang L, Zhu R, Huang Z, Li H, Zhu H. Lipopolysaccharide-induced toll-like receptor 4 signaling in cancer cells promotes cell survival and proliferation in hepatocellular carcinoma. Dig Dis Sci. 2013 Aug;58(8):2223-36.

Wculek SK, Malanchi I. Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature. 2015 Dec 17;528(7582):413-7.

Yamashina S, Ikejima K, Rusyn I, Sato N. Glycine as a potent anti-angiogenic nutrient for tumor growth. J Gastroenterol Hepatol. 2007 Jun;22 Suppl 1:S62-4. 

Yan C, Yang Q, Gong Z. Tumor-Associated Neutrophils and Macrophages Promote Gender Disparity in Hepatocellular Carcinoma in Zebrafish. Cancer Res. 2017 Mar 15;77(6):1395-1407.

Yang Q, Yan C, Yin C, Gong Z. Serotonin Activated Hepatic Stellate Cells Contribute to Sex Disparity in Hepatocellular Carcinoma. Cell Mol Gastroenterol Hepatol. 2017 Jan 17;3(3):484-499.

Zhao H, Yang L, Baddour J, Achreja A, Bernard V, Moss T, Marini JC, Tudawe T, Seviour EG, San Lucas FA, Alvarez H, Gupta S, Maiti SN, Cooper L, Peehl D, Ram PT, Maitra A, Nagrath D. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. Elife. 2016 Feb 27;5:e10250.


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