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Is the Human Embryo an Organism?
Published in Nicholas Colgrove, Bruce P. Blackshaw, Daniel Rodger, Agency, Pregnancy and Persons, 2023
Broadly speaking, there are two basic patterns of embryogenesis; determinate and regulative. A determinate (or lineage-based or “mosaic”) developmental pattern is characterized by the asymmetric distribution of important maternally derived factors in the zygote, combined with a regular pattern of early cell divisions that reliably partition these factors into specific cell lineages. In contrast, in a regulative pattern of development, cell-cell interactions are critically important for the specification of cell types. In embryos showing a regulative pattern of development (mammals and most vertebrates; De Robertis 2006), cells are able to respond to novel signals and adopt novel identities until they ultimately become “committed” to a specific developmental fate (in mammals, at approximately the 16–32 cell stage; Suwińska et al. 2008). It is important to point out that in normal development, signals controlling the formation of specific cell types are generated in an orderly manner by the embryo itself as a component of a self-organized developmental process.
Filler Materials: Indications, Contraindications, and Special Considerations in Oncology Patients
Published in Paloma Tejero, Hernán Pinto, Aesthetic Treatments for the Oncology Patient, 2020
In addition, before complete degradation, you can see the following: High-molecular-weight HA fragments in heavy chains: Mw (Mw >500 kDa) are “space-filling” molecules involved in normal biological processes, with antiangiogenic and “immunosuppressive” properties. Generally, they are associated with inhibition of cell differentiation by suppressing cell-cell interactions or by binding to cell surface receptors.Shorter fragments of HA (Mw = 20–200 kDa): These have pro-inflammatory activity, immunostimulants, and angiogenic properties.
Influence of Cryptorchidism on Leydig Cell Function
Published in Tom O. Abney, Brooks A. Keel, The Cryptorchid Testis, 2020
There is growing evidence for the existence of a relationship between Leydig cells and other testicular cell types (see Chapter 8). It has been postulated that Leydig cell function is controlled to some extent by factors (paracrine substances) from the seminiferous tubules (either germ cells or Sertoli cells). Thus, a series of complex cell-cell interactions are believed to exist, in which function by one cell type is influenced by one or several other cell types. Leydig cell function is conceivably regulated by germ cells, Sertoli cells, myoid cells, and/or other cells. It follows, then, that cryptorchid-induced damage to the tubular compartment can alter this intercellular regulation. This raises the interesting question as to whether cryptorchid-induced changes in Leydig cell function are primary in nature or represent secondary alterations which result from altered paracrine regulatory mechanisms.
Using 3D in vitro cell culture models in anti-cancer drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Spheroid cultures generally are easy 3D cell culture techniques that, despite some of their drawbacks, have been moving toward applications in high-throughput drug discovery [for comprehensive reviews see [2,50,51,72–74]]. Many cancer cells commonly cultured as monolayers adapt well to spheroid culture. Tumor spheroid models derived from established cell lines as well as those obtained through ex vivo propagation of tumors from individual patients (tumor organoids) have been established for a variety of tumor types. Spheroid formation relies on the self-aggregation of cells when cultured in the absence of an attachment surface. They are suited to study molecular and cellular mechanisms of cell–cell interactions when cells aggregate and the role of cell-cell adhesion molecules in cancer cell proliferation and drug response. With this, spheroids may be applicable in cancer drug discovery approaches targeting these intercellular interactions (tumor-tumor, tumor-fibroblast, tumor-immune cell, etc.) and the intracellular signaling pathways that are activated when cells engage with each other. However, it is important to note that cell aggregation alone is not representative of in vivo tumors. To be a more relevant representative of in vivo tumors, spheroid models will require culture for prolonged times to allow for spheroid formation through cell proliferation rather than cell aggregation. Drug discovery in cell aggregates over spheroids formed through proliferating cells and without an ECM-based tumor microenvironment may introduce biases regarding the ability of drug candidates to be effective in vivo.
Lymphocytes in Peritumoral Stroma: Evaluation in Epithelial Ovarian Neoplasms
Published in Immunological Investigations, 2020
Cid Almeida de Lima, Millena Prata Jammal, Renata Margarida Etchebehere, Eddie Fernando Candido Murta, Rosekeila Simões Nomelini
The presence of TILs in the stromal compartment is an important factor because distinct cell groupings in the stroma later create a tumor-specific microenvironment through matrix rearrangement that promotes carcinogenesis, resulting in cell proliferation, invasion, and survival. These activities are orchestrated by cell–cell interaction (Bremnes et al., 2011). Our study demonstrated a greater presence of stromal CD3 cells in patients with primary malignant ovarian neoplasms than in those with benign neoplasms. Similarly, CD3 T lymphocytes were found to be abundant in samples of tumor tissue, ascites, and peripheral blood in a recent study. The authors reported that the higher concentrations of these cells were associated with stage IV relative to stage III ovarian malignancy, and thus reflected a worse prognosis (Rådestad et al., 2018).
The bone marrow stromal niche: a therapeutic target of hematological myeloid malignancies
Published in Expert Opinion on Therapeutic Targets, 2020
Lena Behrmann, Jasmin Wellbrock, Walter Fiedler
Myeloid malignancies remain a life-threatening malignancy with a high need of new therapeutic options. Large genetic and epigenetic studies of MDS, MPN, and AML identified intrinsic alterations, which perturb key processes of hematopoietic development, leading to uncontrolled proliferation, differentiation, apoptosis, and self-renewal. But irrespective of this knowledge, therapeutic options are still limited and prognosis for most patients devastating. Since interactions between leukemic and microenvironmental cells in the bone marrow niche are essential for survival, proliferation, and chemotherapy resistance of leukemic blasts, inhibition of these mechanisms may represent a novel therapeutic approach. These include blockade of cytokine signals as well as cell-cell interactions. Several targetable receptor-ligand systems have been identified in MDS, MNP, and AML and clinical trials have been initiated or completed. These include studies of inhibitors against the CXCR4-CXCL12 or VLA-4-VCAM-1 axes. However, these compounds may not be sufficiently active when used as monotherapy, but require combination with conventional chemotherapy.