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Characteristics, Events, and Stages in Tumorigenesis
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
Introduction of the following four genes; Oct-3/4, Sox2, c-Myc, and KLF4 into a rodent fibroblast population to generate colonies with stem cell characteristics (i.e., embryonic stem cells (ESCs)) was first demonstrated by Takahashi and Yamanaka [812, 813]. Subsequently, these colonies differentiated into endodermal, ectodermal, and mesodermal lineages upon transplantation in immunodeficient rodents, and therefore, termed as induced pluripotent cells (iPSCs) [812]. In addition, Briggs and King demonstrated the possibility of the reversal of cell differentiation (i.e., dedifferentiate: the ability of a cell that is terminally differentiated to go back to a less-differentiated state from within its own lineage [814]) [812, 815]. These findings challenged the unidirectional developmental model of cells. Since then, ESCs have received special attention in the field of regenerative medicine, because of their pluripotent nature [812]. Furthermore, stem cells also harbor the plasticity to transdifferentiate into other lineages and cell types apart from their capabilities of self-sustenance and differentiation into expected lineages [812]. Differentiation, dedifferentiation, and transdifferentiation are all naturally occurring physiological phenomena [814, 816].
Thyroid and Parathyroid Pathology
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, Scott-Brown's Essential Otorhinolaryngology, 2022
Anaplastic carcinoma is a highly malignant tumour typically seen in elderly patients that has a high mortality. It can arise de novo or result from dedifferentiation of an existing neoplasm. It is usually widely invasive and inoperable at presentation. The pathology varies, with the two main patterns being epithelioid and sarcomatoid.
Breast Imaging with Radiolabeled Estrogen Receptor Ligands
Published in Raymond Taillefer, Iraj Khalkhali, Alan D. Waxman, Hans J. Biersack, Radionuclide Imaging of the Breast, 2021
Klemens Maria Scheidhauer, Anton Scharl
Positive ER status is a determining factor for the success of hormone therapy and for prognostication. The mammary gland normally contains hormone receptors; the concentration is markedly raised in more than 50% of mammary carcinomas [16,17]. The pattern of growth of mammary carcinomas can be influenced by changes in the hormonal milieu. Endocrine therapy is effective against receptor-negative tumors in only 10% of patients, while for receptor-positive carcinomas, a successful outcome can be expected in 40% to 70% of cases [18-20]. The receptor content of the cells decreases with increasing dedifferentiation, and can also be influenced by endocrine, chemo-, or radiation therapy [21,22]. Detection of endocrine receptors and receptor-oriented endocrine therapy have now become standard methods for diagnosis and treatment of breast cancer patients [20].
Risk Model Development and Validation in Clinical Oncology: Lessons Learned
Published in Cancer Investigation, 2023
Gary H. Lyman, Pavlos Msaouel, Nicole M. Kuderer
When developing a prognostic risk model, the candidate variables can be pre-specified based on prior knowledge of the background subject matter (2,3,42,43). For example, it is well established clinically and biologically that sarcomatoid dedifferentiation is associated with poor prognostic in patients with renal cell carcinomas (44). Therefore, the presence or absence of sarcomatoid dedifferentiation can be chosen a priori as a prognostic variable in risk models of renal cell carcinomas. Causal diagrams such as directed acyclic graphs (DAGs) may be used to explicitly represent contextual causal knowledge and identify the best sets of variables to include in the risk model (42,45). Variable selection approaches can then be performed in the prespecified model to develop the final risk model (45–47).
Adopting an alternative structure for clinical trials in immunotherapy
Published in Expert Review of Anticancer Therapy, 2021
Evanthia T. Roussos Torres, Alan L. Epstein
In this insightful and original paper, the authors point out that much of the large data sets derived from OMICs analyses are gathered by small translational clinics, or just smaller studies, in which data are generated for individual patients. They first point out that this has shown to be more effective in identifying new combinations of therapies that treat the dominant changes seen in the tumor microenvironment (TME) which defeat effective immune responses mounted by patients. After all, viewed in another way, all cancers only exist regardless of their origin when they override the immune system. The type of cancer, its state of dedifferentiation, its ability to spread and other attributes only are seen when immunity is made ineffectual by the growing tumor. In some regards, it makes great sense that investigations should focus on learning how this occurs and what treatments can be used to reverse this effect to treat cancer effectively. Since data are now showing that each patient or small groups of patients fall into specific categories in this regard, the generation of data by small groups and individual patients that can be analyzed by computational science to identify likely diagnostic and therapeutic parameters for individuals now makes a great deal of sense. This paper highlights that deep correlative analyses of fewer patients have become more feasible in part due to the high cost of these newer types of technology such as single-cell RNA sequencing and spatial transcriptomic evaluations.
Role of artificial intelligence and vibrational spectroscopy in cancer diagnostics
Published in Expert Review of Molecular Diagnostics, 2020
Ihtesham U. Rehman, Rabia Sannam Khan, Shazza Rehman
Most cancers (approximately 90%) are carcinomas. This can be explained by two factors: cell proliferation mainly occurs in epithelia, and they are more frequently exposed to various forms of physical and chemical damage that favor the development of cancer [3]. Dedifferentiation or anaplasia denotes the loss of normal characteristics, which may be attributed to chemical structure and these chemical structures can be very well studied with the use of spectroscopic techniques. These techniques can help in identifying and establishing a chemical pathway by which the cancer progresses. The biological pathway of cancer progression is very well established, but the chemical pathway is still a matter of debate. It is strongly believed that vibrational spectroscopy offers excellent potential to study the chemical structural characteristics of the biological tissues. This is only possible if the spectral bands are precisely and accurately assigned to specific chemical bonds and functional groups.