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Article: Comment on "The process of metastasisation for breast cancer" by J. Engel, R. Eckel, J. Kerr et al.

Demicheli, R / Retsky, M W

European journal of cancer (Oxford, England : 1990)

2004 Volume 40, Issue 4, Page(s) 619–20; author reply 621–3

MeSH term(s)	Breast Neoplasms/pathology ; Female ; Humans ; Models, Biological ; Neoplasm Metastasis/pathology
Language	English
Publishing date	2004-03
Publishing country	England
Document type	Comment ; Letter
ZDB-ID	82061-1
ISSN	1879-0852 ; 0959-8049 ; 0277-5379 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0959-8049 ; 0277-5379 ; 0964-1947
DOI	10.1016/j.ejca.2003.09.038
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Article ; Online: Reimagining Cancer: Moving from the Cellular to the Tissue Level.

Demicheli, Romano / Hrushesky, William J M

Cancer research

2022 Volume 83, Issue 2, Page(s) 173–180

Abstract: The current universally accepted explanation of cancer origin and behavior, the somatic mutation theory, is cell-centered and rooted in perturbation of gene function independent of the external environmental context. However, tumors consist of various ... ...

Abstract	The current universally accepted explanation of cancer origin and behavior, the somatic mutation theory, is cell-centered and rooted in perturbation of gene function independent of the external environmental context. However, tumors consist of various epithelial and stromal cell populations temporally and spatially organized into an integrated neoplastic community, and they can have properties similar to normal tissues. Accordingly, we review specific normal cellular and tissue traits and behaviors with adaptive temporal and spatial self-organization that result in ordered patterns and structures. A few recent theories have described these tissue-level cancer behaviors, invoking a conceptual shift from the cellular level and highlighting the need for methodologic approaches based on the analysis of complex systems. We propose extending the analytical approach of regulatory networks to the tissue level and introduce the concept of "cancer attractors." These concepts require reevaluation of cancer imaging and investigational approaches and challenge the traditional reductionist approach of cancer molecular biology.
MeSH term(s)	Humans ; Neoplasms/genetics ; Neoplasms/pathology
Language	English
Publishing date	2022-10-20
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-22-1601
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Article ; Online: From Oncological Paradigms to Non-Communicable Disease Pandemic. The Need of Recovery Human Biology Evolution.

Biganzoli, Elia / Demicheli, Romano

International journal of environmental research and public health

2021 Volume 18, Issue 19

Abstract: The paradigm of the Somatic Mutation Theory (SMT) is failing, and a new paradigm is underway but not yet established. What is being challenged is a conceptual approach that involves the entire human biology and the development of chronic diseases. The ... ...

Abstract	The paradigm of the Somatic Mutation Theory (SMT) is failing, and a new paradigm is underway but not yet established. What is being challenged is a conceptual approach that involves the entire human biology and the development of chronic diseases. The behavior of breast and other solid cancers is compatible with the concept that the primary tumor is able to control its microscopic metastases, in the same way that an organ (e.g., the liver) is able to control its physiological size. This finding suggested that cancer and its metastases may behave as an organoid. The new paradigm under construction considers the origin of tumors as a disturbance in the communication network between tissue cell populations and between cells and extracellular matrix, and supports a systemic approach to the study of both healthy and pathologic tissues. The commentary provides a rationale for the role of physical exercise in the control of tumor dormancy according to a human evolutionary perspective.
MeSH term(s)	Biology ; Humans ; Neoplasms/epidemiology ; Noncommunicable Diseases/epidemiology ; Pandemics
Language	English
Publishing date	2021-09-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph181910087
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Article: Late Recurrence in Breast Cancer: To Run after the Oxen or to Try to Close the Barn?

Demicheli, Romano / Biganzoli, Elia

Cancers

2021 Volume 13, Issue 9

Abstract: The problem of late recurrence in breast cancer has recently gained attention and was also addressed in an international workshop held in Toronto (ON, Canada), in which several aspects of the question were examined. This Commentary offers a few ... ...

Abstract	The problem of late recurrence in breast cancer has recently gained attention and was also addressed in an international workshop held in Toronto (ON, Canada), in which several aspects of the question were examined. This Commentary offers a few considerations, which may be useful for the ongoing investigations. A few premises are discussed: (a) clinical recurrences, especially the late ones, imply periods of tumor dormancy; (b) a structured pattern of distant metastases appearance is detectable in both early and late follow-up times; (c) the current general paradigm underlying neoplastic treatments, i.e., that killing all cancer cells is the only way to control the disease, which is strictly sprouting from the somatic mutation theory, should be re-considered. Finally, a few research approaches are suggested.
Language	English
Publishing date	2021-04-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13092026
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Article: Comment to "Effect of primary tumor extirpation in breast cancer patients who present with stage IV disease and intact primary tumor" by G V Babiera, R Rao, L Feng, F Meric-Bernstam, H M Kuerer, S E Singletary, K K Hunt, M I Ross, K M Gwyn, B W Feig, F C Ames, G N Horthobagyi. Ann Surg Oncol 2006;13:776-782.

Demicheli, Romano / Hrushesky, William J M / Retsky, Michael W / Bonadonna, Gianni / Valagussa, Pinuccia

Annals of surgical oncology

2007 Volume 14, Issue 4, Page(s) 1519–1520

MeSH term(s)	Bone Neoplasms/secondary ; Bone Neoplasms/surgery ; Breast Neoplasms/pathology ; Breast Neoplasms/surgery ; Disease Progression ; Female ; Humans ; Liver Neoplasms/secondary ; Liver Neoplasms/surgery ; Lung Neoplasms/secondary ; Lung Neoplasms/surgery ; Mastectomy ; Neoplasm Recurrence, Local ; Prognosis ; Survival Rate
Language	English
Publishing date	2007-04
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-006-9279-2
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Article: Does Physical Activity Have an Impact on Recurrence Dynamics in Early Breast Cancer Patients?

Biganzoli, Elia / Desmedt, Christine / Demicheli, Romano

Journal of clinical medicine

2021 Volume 10, Issue 4

Abstract: Several studies have suggested that pre and/or postdiagnosis physical activity can reduce the risk of recurrence in breast cancer patients, however its effect according to follow-up time has not yet been investigated. We analyzed recurrence and mortality ...

Abstract	Several studies have suggested that pre and/or postdiagnosis physical activity can reduce the risk of recurrence in breast cancer patients, however its effect according to follow-up time has not yet been investigated. We analyzed recurrence and mortality dynamics in randomized clinical trials (RCTs) from Australia and Canada. The combined Australian RCTs evaluated, at a median follow-up of 8.3 years, an 8-month pragmatic exercise intervention in 337 women with newly diagnosed breast cancer, while the Canadian RCT evaluated, at a median follow-up of 7.4 years, supervised aerobic or resistance exercise during chemotherapy in 242 patients. For each RCT, the control arm consisted of patients undergoing usual care. We estimated the event dynamics by the discrete hazard function, through flexible regression of yearly conditional event probabilities with generalized additive models. In the considered RCTs, the recurrence and mortality risk of patients enrolled in the physical activity arm were stably decreased at medium/long term after five year of follow-up. In the Australian RCTs where patients were recruited by urban versus rural area, the latter group did not display benefit from physical activity. Estimated odds ratios (95% confidence intervals) for disease-free survival (DFS) in urban women were 0.63 (0.22-1.85); 0.27 (0.079-0.90); 0.11 (0.013-0.96) at the 3rd, 5th and 7th year of follow-up, respectively. For rural women, DFS patterns were overlapping with odds ratios (ORs), approximating 1 at the different years of follow-up. Although not reaching statistical evidence, the estimates in the Canadian trial were in line with the results from the Australian urban women with ORs (95% CI) for DFS of 0.70 (0.33-1.50); 0.47 (0.19-1.18); 0.32 (0.077-1.29) at 3rd, 5th, 7th follow-up year, respectively. While we acknowledge that the analyzed RCTs were not designed for investigating disease recurrence over time, these results support the evidence that physical activity reduces the risk of developing medium-/long-term metastases. Additional translational research is needed to clarify the mechanisms underlying these observations.
Language	English
Publishing date	2021-02-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10040831
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Article ; Online: Tumours and tissues: similar homeostatic systems?

Demicheli, Romano

Targeted oncology

2013 Volume 8, Issue 2, Page(s) 97–105

Abstract: The currently prevalent somatic mutation theory of carcinogenesis and metastases explicitly assumes that cancer is a cellular disease, i.e. a disease of the control of cell proliferation and/or cell differentiation. Accordingly, explanations should ... ...

Abstract	The currently prevalent somatic mutation theory of carcinogenesis and metastases explicitly assumes that cancer is a cellular disease, i.e. a disease of the control of cell proliferation and/or cell differentiation. Accordingly, explanations should always be sought for at a gene and/or gene product level, regardless of the level of organization at which the phenomenon is observed. Such a reductionist approach characterized the century-old effort to find cancer cell singularities, absent in normal cells, without apparent success, however. More recently alternative views have been put forward, assuming that cancer is a tissue-based disease involving disturbed interactions within the tissue architecture. In this review, selected reports on normal tissue homeostasis and bone marrow contribution to both tumour cells and tumour stroma are reviewed. Regarding normal tissues, the existence of a complex homeostatic system actually involving the whole organism emerges. Regarding tumours, remarkable similarities with normal tissue activities are apparent, providing some evidence that tumours share many biological features and processes with normal tissues. The review supports the concept that cancer is a tissue-based disease and that its pathological nature may result from unbalanced/untimely activation of otherwise normal physiological processes.
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Cell Growth Processes/genetics ; Homeostasis/genetics ; Humans ; Neoplasms/genetics ; Neoplasms/pathology
Language	English
Publishing date	2013-05-02
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	2222136-0
ISSN	1776-260X ; 1776-2596
ISSN (online)	1776-260X
ISSN	1776-2596
DOI	10.1007/s11523-013-0277-6
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Article ; Online: From Oncological Paradigms to Non-Communicable Disease Pandemic. The Need of Recovery Human Biology Evolution

Elia Biganzoli / Romano Demicheli

International Journal of Environmental Research and Public Health, Vol 18, Iss 10087, p

2021 Volume 10087

Abstract	The paradigm of the Somatic Mutation Theory (SMT) is failing, and a new paradigm is underway but not yet established. What is being challenged is a conceptual approach that involves the entire human biology and the development of chronic diseases. The behavior of breast and other solid cancers is compatible with the concept that the primary tumor is able to control its microscopic metastases, in the same way that an organ (e.g., the liver) is able to control its physiological size. This finding suggested that cancer and its metastases may behave as an organoid. The new paradigm under construction considers the origin of tumors as a disturbance in the communication network between tissue cell populations and between cells and extracellular matrix, and supports a systemic approach to the study of both healthy and pathologic tissues. The commentary provides a rationale for the role of physical exercise in the control of tumor dormancy according to a human evolutionary perspective.
Keywords	cancer dormancy ; low-grade chronic inflammation ; healthy aging ; physical exercise ; Medicine ; R
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: Supramolecular assemblies from antimony(V) complexes for the treatment of leishmaniasis.

Demicheli, Cynthia / Vallejos, Virgínia M R / Lanza, Juliane S / Ramos, Guilherme S / Do Prado, Bruno R / Pomel, Sébastien / Loiseau, Philippe M / Frézard, Frédéric

Biophysical reviews

2023 Volume 15, Issue 4, Page(s) 751–765

Abstract: The pentavalent meglumine antimoniate (MA) is still a first-line drug in the treatment of leishmaniasis in several countries. As an attempt to elucidate its mechanism of action and develop new antimonial drugs with improved therapeutic profile, Sb(V) ... ...

Abstract	The pentavalent meglumine antimoniate (MA) is still a first-line drug in the treatment of leishmaniasis in several countries. As an attempt to elucidate its mechanism of action and develop new antimonial drugs with improved therapeutic profile, Sb(V) complexes with different ligands, including β-cyclodextrin (β-CD), nucleosides and non-ionic surfactants, have been studied. Interestingly, Sb(V) oxide, MA, its complex with β-CD, Sb(V)-guanosine complex and amphiphilic Sb(V) complexes with N-alkyl-N-methylglucamide, have shown marked tendency to self-assemble in aqueous solutions, forming nanoaggregates, hydrogel or micelle-like nanoparticles. Surprisingly, the resulting assemblies presented in most cases slow dissociation kinetics upon dilution and a strong influence of pH, which impacted on their pharmacokinetic and therapeutic properties against leishmaniasis. To explain this unique property, we raised the hypothesis that multiple pnictogen bonds could contribute to the formation of these assemblies and their kinetic of dissociation. The present article reviews our current knowledge on the structural organization and physicochemical characteristics of Sb-based supramolecular assemblies, as well as their pharmacological properties and potential for treatment of leishmaniasis. This review supports the feasibility of the rational design of new Sb(V) complexes with supramolecular assemblies for the safe and effective treatment of leishmaniasis.
Language	English
Publishing date	2023-06-06
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2486483-3
ISSN	1867-2469 ; 1867-2450
ISSN (online)	1867-2469
ISSN	1867-2450
DOI	10.1007/s12551-023-01073-6
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Article ; Online: Interpreting Breast Cancer Survival Data by the Hazard Function: Remarkable Findings from Event Dynamics.

Demicheli, Romano / Hrushesky, William / Retsky, Michael / Biganzoli, Elia

Medicina (Kaunas, Lithuania)

2020 Volume 56, Issue 9

Abstract: The report addresses the role of the hazard function in the analysis of disease-free survival data in breast cancer. An investigation on local recurrences after mastectomy provided evidence that uninterrupted growth is inconsistent with clinical findings ...

Abstract	The report addresses the role of the hazard function in the analysis of disease-free survival data in breast cancer. An investigation on local recurrences after mastectomy provided evidence that uninterrupted growth is inconsistent with clinical findings and that tumor dormancy could be assumed as working hypothesis to understand the clinical course of the disease. Additionally, it was deemed that the lag-time between primary tumor removal and tumor recurrence is dynamically dependent on the subclinical metastasis development within the host-tumor system and, therefore, may be informative about the biology of the disease. Accordingly, the hazard function, which estimates the event risk pattern through the time, was adopted to analyze survival data. The multipeak pattern of the hazard function suggested that the process metastasis development has discontinuous features. A new paradigm of breast cancer metastatic development was proposed, involving the notions of tumor homeostasis, tumor quiescence in specific metastatic microscopic phases and surgery-related acceleration of the metastatic process. All analyses by prognostic factors (e.g., by menopausal status) or treatment modalities (e.g., by adjuvant chemotherapy) or other parameters (e.g., site of metastasis), provided coherent data in agreement with the model. The hazard rate function allowed addressing several clinical questions including meaning of ipsilateral breast tumor recurrence (IBTR), oncologic effect of delayed breast reconstruction, surgery related metastasis acceleration, possible role of anti-inflammatory drugs and body mass index (BMI) to modulate the recurrence risk. We conclude that the hazard function is a powerful tool to investigate the post-surgical course of early breast cancer and other operable tumors and to make inferences on their biology.
MeSH term(s)	Breast Neoplasms/drug therapy ; Breast Neoplasms/surgery ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Humans ; Mastectomy ; Neoplasm Recurrence, Local
Language	English
Publishing date	2020-09-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2188113-3
ISSN	1648-9144 ; 1010-660X
ISSN (online)	1648-9144
ISSN	1010-660X
DOI	10.3390/medicina56090468
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