Effect of film size on production of foreign body sarcoma by perforated film implants

Iomhair, Maura Mhic; Lavelle, S. M.

doi:10.3233/thc-1997-5406

Cited by 8 publications

(3 citation statements)

References 19 publications

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“…Although the aforementioned evidence points to pore size alone, without its impact on charge, surface area, or roughness, as the most likely explanation for differences in incidences of sarcomas, a more definitive study could be conducted. A potential study design is a 2 × 2 × 2 × 2 factorial experiment involving 128 mice with the following four factors: pore size (0.025 μm versus 0.45 μm), roughness (two levels, perhaps either roughening or no roughing of the filter surface or a smooth or rough plastic lattice overlay related to [ 31 ]), surface area (either a single filter or a stacked pair of filters as in [ 32 ]), and electrostatic charge (two levels, perhaps hydrophobic versus normal filters as in [ 33 ]), The sample size of 8 per each of 16 groups is designed to an detect extreme interactions, namely a comparison between 9/10 in one group versus 1/10 in another group with power of .80 and Bonferroni type I error of .05/15, for 15 comparisons versus a reference group. However we recommend analysis via logistic regression to more systematically evaluate the factors.…”

Section: Discussionmentioning

confidence: 99%

Paradoxes in carcinogenesis: New opportunities for research directions

Baker

Kramer

2007

BMC Cancer

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Background: The prevailing paradigm in cancer research is the somatic mutation theory that posits that cancer begins with a single mutation in a somatic cell followed by successive mutations. Much cancer research involves refining the somatic mutation theory with an ever increasing catalog of genetic changes. The problem is that such research may miss paradoxical aspects of carcinogenesis for which there is no likely explanation under the somatic mutation theory. These paradoxical aspects offer opportunities for new research directions that should not be ignored. Discussion:Various paradoxes related to the somatic mutation theory of carcinogenesis are discussed: (1) the presence of large numbers of spatially distinct precancerous lesions at the onset of promotion, (2) the large number of genetic instabilities found in hyperplastic polyps not considered cancer, (3) spontaneous regression, (4) higher incidence of cancer in patients with xeroderma pigmentosa but not in patients with other comparable defects in DNA repair, (5) lower incidence of many cancers except leukemia and testicular cancer in patients with Down's syndrome, (6) cancer developing after normal tissue is transplanted to other parts of the body or next to stroma previously exposed to carcinogens, (7) the lack of tumors when epithelial cells exposed to a carcinogen were transplanted next to normal stroma, (8) the development of cancers when Millipore filters of various pore sizes were was inserted under the skin of rats, but only if the holes were sufficiently small. For the latter paradox, a microarray experiment is proposed to try to better understand the phenomena. Summary:The famous physicist Niels Bohr said "How wonderful that we have met with a paradox. Now we have some hope of making progress." The same viewpoint should apply to cancer research. It is easy to ignore this piece of wisdom about the means to advance knowledge, but we do so at our peril.

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Section: Discussionmentioning

confidence: 99%

Paradoxes in carcinogenesis: New opportunities for research directions

Baker

Kramer

2007

BMC Cancer

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“…These implanted materials fall into various categories, including metal, plastic, polymers, millipore filters, nitrocellulose, etc., and are insoluble and not toxic [182][183][184][185][186][187][188]. Moreover, the carcinogenesis does not seem to correlate with the amount (dose) of the implanted materials, but rather is related to their physical shape or surface [176,[188][189][190]. Therefore, the carcinogenesis does not seem to occur via mutations caused by the intake of the materials into the cells but rather occurs due to disturbances to the extracellular milieu (Scenarios b and d in Fig.…”

Section: Dissenting Evidence 2: Altered Extracellular Milieu May Init...mentioning

confidence: 99%

Mutation or not, what directly establishes a neoplastic state, namely cellular immortality and autonomy, still remains unknown and should be prioritized in our research

Zhu¹,

Wang²,

Zellmer³

et al. 2022

J. Cancer

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“…Определение значения разницы в экспрессии других цитокинов в наших экспериментах требует дополнительного изучения. В 1997 г. M. M. Iomhair и S. M. Lavelle показали, что увеличение площади имплантируемых миллипоровых неканцерогеннных фильтров с порами 0,45 мкм в 2 и 3 раза (имплантировались двойные и тройные фильтры) приводит к образованию опухолей в достаточно большом количестве (7 / 30 и 16 / 30 соответственно) [18]. С учетом наших данных возможна следующая интерпретация этой работы.…”

Section: экспериментальные статьиunclassified

Differences in the profile of cytokine expression induced by implantation of oncogenic and non-oncogenic millipore filters

2019

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Background. Clarification of the mechanisms of carcinogenesis induced by foreign bodies is one of the urgent problems of modern oncology. This is due to the fact that there is a relationship between the processes of inflammation and carcinogenesis. Today, there is no doubt the fact that cytokines and signal molecules in the focus of inflammation (products of inflammation) can contribute to the initiation of carcinogenesis, as well as stimulate tumor progression. In the case of carcinogenesis induced by foreign bodies, the key issue is understanding the differences in the body’s response to the implantation of foreign bodies that can cause tumor formation and do not have this ability. One of the phenomena of this type of carcinogenesis is the occurrence of sarcoma after the subcutaneous implantation in mice of hydrophilic millipore filters with a pore diameter not exceeding 0.1 μm and the inability to induce tumors of one’s with a pore diameter greater than or equal to 0.22 μm.The objective of our work was to study the differences between oncogenic and non-oncogenic filters at the molecular level.Materials and methods. Reverse transcription polymerase chain reaction method was used to study the expression of a number of cytokines that are products of macrophage cells that live on the surface of implanted filters and in the surrounding capsule. Filters with pore diameters of 0.025 μm (carcinogenic) and 0.45 μm (non-carcinogenic) were compared in 8, 35 days and 5.5 months after implantation.Results and conclusion. After 8 days we observed significant (p <0.01) excess of expression of two cytokines interleukin 1β (IL-1β) by cells around oncogenic filters (with pore of 0.025 μm) compared to non-oncogenic one’s (with pore of 0.45 μm) After 35 days, significant (p <0.01) excess of expression of IL-1β, Tnf-α, iNOS (induced nitric oxide synthase), and IL-6 by cells around the oncogenic filters (0.025 μm) compared to non-oncogenic one’s (0.45 μm) was observed. There was no quantitative difference in the expression of Nf-κB1 and Nf-κB2 (nuclear factor κ-B1, κ-B2), Tgf-β (transforming growth factor β), IL-10. After 5.5 months the expression of IL-1β by cells on oncogenic filters was still significant; for Tnf-α, iNOS, IL-6 and IL-10 there was no practically difference in expression. For Nf-κB1 and Nf-κB2, Tgf-β and COX-2 (cyclooxygenase 2) the difference was significant, cells on non-oncogenic filters are expressed more then on oncogenic one’s.

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Effect of film size on production of foreign body sarcoma by perforated film implants

Cited by 8 publications

References 19 publications

Paradoxes in carcinogenesis: New opportunities for research directions

Paradoxes in carcinogenesis: New opportunities for research directions

Mutation or not, what directly establishes a neoplastic state, namely cellular immortality and autonomy, still remains unknown and should be prioritized in our research

Differences in the profile of cytokine expression induced by implantation of oncogenic and non-oncogenic millipore filters

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