cancer cell biology and angiogenesis chapter 24

... synthesis and mitosis and in response to environmental mutagens; these repair pathways are often abnormal in cancer cells. When a normal cell has sustained too much damage to repair, the cell activates ... damage to the organ. These cell death pathways are also commonly altered in cancer cells, leading to the survival of damaged cells that would normally die. Cancer cells often exist under conditions ... breast, and pancreatic cancers. Table 80-1 Phenotypic Characteristics of Malignant Cells Deregulated cell proliferation: Loss of negative regulators (suppressor oncogenes, i.e., Rb, p53), and...

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... whether a cell will enter S-phase. The complex of CDK4 or CDK6 with D type cyclins forms a G 1 -specific kinase whose activity is regulated by growth factors, nutrients, and cell- cell and cell- matrix ... targeted therapy of cancer. Therapeutic Approaches to Cell Cycle Abnormalities in Cancer The mechanism of cell division is substantially the same in all dividing cells and has been conserved ... nonmalignant cells, have become possible with advances in the understanding of oncogene and tumor-suppressor pathways. This chapter describes the convergence of scientific, pharmacologic, and medical...

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... technology before the clinical utility of this approach can be fully realized. Chapter 080. Cancer Cell Biology and Angiogenesis (Part 3) Figure 80-1 ... other stimuli, and predisposes cells to chromosome instability. This genomic instability greatly increases the probability that p53 null cells will acquire additional mutations and become malignant. ... transcription factor activity and tumor-suppressor functions, and also result in high intracellular levels of p53 protein. Inactivation of the p53 pathway compromises cell cycle arrest, attenuates...

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... melanoma, prostate, lung, breast, and colon cancer cells in vitro. Clinical trials of telomerase vaccines are underway. Chapter 080. Cancer Cell Biology and Angiogenesis (Part 4) Telomerase ... epithelium, and germ cells) that require extensive cell division to maintain tissue homeostasis. More than 90% of human cancers express high levels of telomerase that prevent telomere exhaustion and ... (e.g., Myc, AP-1, and serum response factor) and the cell cycle machinery (CDKs and cyclins). Inhibitors of many of these pathways have been developed for the treatment of human cancers. Examples...

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... Breast cancer Binds HER2 on tumor cell surface and induces receptor internalization. Cetuximab (Erbitux) EGFR Colon cancer, squamous cell carcinoma of the head and neck Binds extracellular ... Possible activity against BRAF in melanoma, colon cancer, and others. Erlotinib (Tarceva) EGFR Non- small cell lung cancer; pancreatic cancer Competitive inhibitor of the ATP binding ... of EGFR and blocks binding of EGF and TGF- α; induces receptor internalization. Potentiates the efficacy chemotherapy and radiotherapy. Panitumomab (Vectibix) EGFR Colon cancer Like...

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... of tumor cells and induces internalization of the receptor, thereby reducing the level of surface expression. This leads to inhibition of cell cycle progression and renders cancer cells more ... breast cancer patients. The PDGFR and its ligand, platelet-derived growth factor (PDGF), are overexpressed in many glioblastomas and in subsets of melanoma, ovarian, pancreatic, gastric, lung, and ... human cancer, and provide a mechanism to identify subsets of patients likely to respond to the targeted therapy. The wild-type EGFR is expressed by many other human cancers, and in colon cancer...

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... the cancer cell, without harming normal cells (which maintain wild-type function for gene A). High- throughput screens can now be performed using isogenic cell line pairs in which one cell ... transition and passage through the cell cycle. Inhibition of one pathway (such as pathway A by a targeted inhibitor) has no significant effect due to redundancy provi ded by pathways B and C. In cancer ... cancer cells, oncogenic mutations lead over time to dependency on the activated pathway, with loss of significant input from pathways B and C. The dependency or addiction of the cancer cell to...

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... changes that may include growth arrest, differentiation, or apoptosis. Chapter 080. Cancer Cell Biology and Angiogenesis (Part 8) PI3K is a heterodimeric lipid kinase that catalyses ... of Myc, β-catenin, cyclin D1, and cyclin E, and blocking upregulation of p27 Kip1 and Bim (an apoptosis-inducing protein). Furthermore, the growth of cancer cells requires the activation of ... gene expression in cancer cells. Tumor- suppressor genes are often epigenetically silenced in cancer cells. In the upper dephosphorylating PIP 3 , is mutated in many human cancers, leading to...

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... cutaneous T cell lymphoma (e.g., vorinostat) and some solid tumors. HDAC inhibitors may target cancer cells via a number of mechanisms including upregulation of death receptors (DR4/5, FAS, and their ... (DR4/5, FAS, and their ligands) and p21 Cip1/Waf1 , as well as inhibition of cell cycle checkpoints. The pattern of gene transcription is aberrant in all human cancers, and in many cases, epigenetic ... activity of CDK4/cyclin D and rendering pRB nonfunctional. In sporadic forms of renal, breast, and colon cancer, the von Hippel–Lindau (VHL), breast cancer 1 (BRCA1), and serine/threonine kinase...

Ngày tải lên: 07/07/2014, 01:20

... the onl y target for proteasome inhibitors. Chapter 080. Cancer Cell Biology and Angiogenesis (Part 10) Estrogen receptors (ERs) and androgen receptors, members of the steroid hormone ... used to treat breast and prostate cancers, respectively. Tamoxifen, a partial agonist and antagonist of ER function, can mediate tumor regression in metastatic breast cancer and can prevent disease ... intra- and extracellular signals impinge upon the core cell cycle machinery to regulate cell division, so too these signals are transmitted to a core enzymatic machinery that regulates cell death...

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