Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing.
25 Dec 1986-The New England Journal of Medicine (Massachusetts Medical Society)-Vol. 315, Iss: 26, pp 1650-1659
TL;DR: Tumors of epithelioma are composed of two discrete but interdependent compartments: the malignant cells themselves and the stroma that they induce and in which they are dispersed.
Abstract: SOLID tumors are composed of two discrete but interdependent compartments: the malignant cells themselves and the stroma that they induce and in which they are dispersed.1 , 2 In tumors of epitheli...
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TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
51,099 citations
Cites background from "Tumors: wounds that do not heal. Si..."
...Inflammation Pathologists have long recognized that some tumors are densely infiltrated by cells of both the innate and adaptive arms of the immune system and thereby mirror inflammatory conditions arising in non-neoplastic tissues (Dvorak, 1986)....
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...Such work traced its conceptual roots back to the association of sites of chronic inflammation with tumor formation, and to the observation that tumors could be portrayed as wounds that never heal (Schäfer and Werner, 2008: Dvorak, 1986)....
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TL;DR: It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration.
Abstract: Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.
12,395 citations
TL;DR: The principal mechanisms that govern the effects of inflammation and immunity on tumor development are outlined and attractive new targets for cancer therapy and prevention are discussed.
8,664 citations
Cites background from "Tumors: wounds that do not heal. Si..."
...…and cancer, enterocytes selectively lose expres- 888 Cell 140, 883–899, March 19, 2010 ª2010 Elsevier Inc. sion of components involved in mismatch repair, namely MLH1 and PMS2, as a result of histone deacetylase- and DEC-1-mediated epigenetic repression of the Mlh1 promoter (Edwards et al., 2009)....
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TL;DR: Think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth, which may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.
Abstract: Recent discoveries of endogenous negative regulators of angiogenesis, thrombospondin, angiostatin and glioma-derived angiogenesis inhibitory factor, all associated with neovascularized tumours, suggest a new paradigm of tumorigenesis. It is now helpful to think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth. The extent to which the negative regulators are decreased during this switch may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.
7,916 citations
TL;DR: A rationale for the use of cytokine and chemokine blockade, and further investigation of non-steroidal anti-inflammatory drugs, in the chemoprevention and treatment of malignant diseases is provided.
6,905 citations
References
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Book•
01 Jan 1974
TL;DR: The objective is to establish an experimental procedure and show direct AFM progression from EMT to EMT using a simple, straightforward, and reproducible procedure.
Abstract: Pathologic basis of disease , Pathologic basis of disease , کتابخانه دیجیتالی دانشگاه علوم پزشکی و خدمات درمانی شهید بهشتی
5,162 citations
TL;DR: Tumor ascites fluids from guinea pigs, hamsters, and mice contain activity that rapidly increases microvascular permeability, and this activity is secreted by these tumor cells and a variety of other tumor cell lines in vitro.
Abstract: Tumor ascites fluids from guinea pigs, hamsters, and mice contain activity that rapidly increases microvascular permeability. Similar activity is also secreted by these tumor cells and a variety of other tumor cell lines in vitro. The permeability-increasing activity purified from either the culture medium or ascites fluid of one tumor, the guinea pig line 10 hepatocarcinoma, is a 34,000- to 42,000-dalton protein distinct from other known permeability factors.
3,936 citations
TL;DR: This chapter describes two types of plasminogen activators—namely, the urokinase-type plasMinogen activator (u-PA) and the tissue- type plasmineg activator(t-PA), which are essentially different gene products.
Abstract: Publisher Summary This chapter discusses the role of plasminogen activators in various biological processes. In specific, it describes two types of plasminogen activators—namely, the urokinase-type plasminogen activator (u-PA) and the tissue-type plasminogen activator (t-PA), which are essentially different gene products. The amino acid sequences of these activators and nucleotide sequences of the corresponding cDNAs have largely been determined, and the cDNAs have been cloned using recombinant techniques. A variety of enzymatic as well as immunological assay and detection methods have also been developed that allows a precise quantification of the activators, a distinction between u-PA and t-PA, determination of whether an activator is present in its active or zymogen form, analysis of the kinetics of different steps of the cascade reaction, and immunocytochemical identification of u-PA and t-PA in tissue sections. Much of the studies on plasminogen activators and cancer has been guided by the hypothesis that proteolysis of the components of extracellular matrix, initiated by the release of plasminogen activator from the cancer cells, plays a decisive role for the degradation of normal tissue, and thereby for invasive growth and metastases.
2,545 citations
TL;DR: The biology of platelet derived growth factor, it will really give you the good idea to be successful.
1,999 citations
Journal Article•
TL;DR: The role of the macrophage in wound repair has been investigated by studying the healing process in wounds depleted of this cell and/or its phagocytic activity as discussed by the authors, where hydrocortisone acetate administered as a subcutaneous depot was used to induce a prolonged monocytopenia in guinea pigs, and antimacrophage serum (AMS) was used for local elimination of tissue macrophages.
Abstract: The role of the monocyte/macrophage in wound repair has been investigated by studying the healing process in wounds depleted of this cell and/or its phagocytic activity. Hydrocortisone acetate (0.6 mg/g body weight) administered as a subcutaneous depot was used to induce a prolonged monocytopenia in guinea pigs, and antimacrophage serum (AMS) was used for local elimination of tissue macrophages. In vitro, the presence of complement, macrophages are rapidly lysed and used killed by AMS. In the absence of complement, AMS is not cytotoxic but potently inhibits adherence to and phagocytosis of opsonized erythrocytes by macrophages. AMS titers were obtained by observation of adherence and phagocytosis of opsonized erythrocytes in serial dilutions of AMS. Six groups of animals were studied: a) untreated animals, b)animals receiving daily subcutaneous injections of normal rabbit serum (NRS) around each wound, c)animals receiving daily subcutaneous AMS around each wound, d)animals receiving systemic hydrocortisone, e)animals receiving systemic hydrocortisone and daily injections of NRS around each wound, and f)animals receiving systemic hydrocortisone and daily AMS around each wound. Wounds consisted of a series of six linear incisions in the dorsal skin. Subcutaneous AMS alone has no effect on the number of circulating monocytes, nor was there any observable effect on the number or the phagocytic ability of wound macrophages. Fibrosis in these wounds was unaffected. Systemic hydrocortisone induced a prolonged monocytopenia. The macrophage level in the wounds of these monocytopenic animals was reduced to approximately one-third that of controls; the phagocytic activity of the monocytes/macrophages that did appear in these wounds was, however, similar to that of controls. Some inhibition of wound debridement was observed in these wounds, but fibrosis was virtually unaffected. Collagen synthesis, as judged morphometrically, was similar to that of control wounds at all stages of repair. Conjoint systemic hydrocortisone and subcutaneous AMS around each wound resulted in the almost complete disappearance of macrophages from the wounds. Wound fibrin levels were elevated, and clearance of fibrin, neutrophils, erythrocytes and other miscellaneous debris from these wounds was delayed. Fibroblasts, which in control wounds first appear by 3 days postwounding and reach maximal levels by day 5, did not appear in these wounds until day 5, and their subsequent rate of proliferation was slower than that of controls. Continued.
1,449 citations