Malignancy circulating cancer cells

Blood vessels penetrating tumors provide malignant cells with another point at which to enter the circulation. Evidence exists that in situation where cancers disseminate predominantly by the blood, the extent of metastasis depends upon the vasculature of the primary tumor. Thin-walled capillaries, especially those newly formed, provide poor resistance to invading cancer cells. Also, data from microscopy studies show that the endothelium of tumor vessels, particularly in areas of poor oxygenation, is often abnormal (Kl). These abnormalities may permit invasion by neoplastic cells (P3). Finally, tumors can spread by direct extension into body cavities such as pleural and peritoneal spaces. An example of this is the formation of peritoneal metastases from ovarian carcinoma. 

In addition to the cellular expression on malignant blast cells in AML, elevated levels of suPAR were found in plasma from leukemia patients [18]. In a longitudinal study, in which patients receiving chemotherapy were monitored, it was demonstrated that the suPAR level in plasma from patients with AML correlated with the number of circulating tumor cells and that these were reduced after chemotherapy. In plasma from AML patients, suPAR(II III) was detected in addition to intact suPAR. This is in contrast to findings in plasma from healthy individuals and from the ovarian cancer patients described above [144]. suPAR(II III) was also present in plasma made from bone marrow aspirates. The other cleaved form, uPAR(I), was only identified in urine. Lysates of the leukemic cells contained both intact uPAR and uPAR(II-III). The amounts of suPAR(II III) in plasma and uPAR(I) in urine were decreased following chemotherapy. In healthy controls, intact uPAR was detected in lysates from mononuclear cells in blood and suPAR(I-III) in plasma and bone marrow aspirates, while suPAR(II-III) was detected in urine [18]. 

Since the publication of the original articles by Smith et al. in 1991 on the detection of circulating tumor cells in the malignant melanoma patients (SIO), many investigators have analyzed circulating tumor cells in the peripheral blood of patients with a variety of solid tumors by conventional RT-PCR. In this section, we first summarize the results from conventional RT-PCR studies and then refer to recent advances in the detection of circulating tumor cells with the quantitative real-time RT-PCR method. We selected melanoma and colorectal cancers, mainly the latter, which is one of the most extensively studied cancers in this compartment. 

F. Role in therapy Radioimmunotherapy is a promising new area of cancer treatment that combines the targeting power of monoclonal antibodies with the cell-damaging ability of localized radiation. When infused into a patient, these radiation-carrying antibodies circulate in the body until they locate and bind to the surface of specific cells, and then deliver their cytotoxic radiation directly to malignant cells. Zevalin is the first treatment for cancer that includes a monoclonal antibody that is combined... 

Pulmonary gene therapy is attractive for the treatmment of chronic bronchitis, cystic fibrosis, a-1 antitrypsin deficiency, familial emphysema, asthma, pulmonary infections, surfactant deficiency, pulmonary hypertension, lung cancer, and malignant mesothelioma. The pulmonary endothelium may act as a bioreactor for the production and secretion of therapeutic proteins, such as clotting factors and erythropoietin into the blood circulation. There is a potential benefit for acquired lung diseases, as well as cancers, to be controlled and possibly treated by expression of cytokines, surfactant, antioxidant enzymes, or mucoproteins within lung cells. 

The presence of tumor-derived DNA in the plasma of cancer patients has inspired researchers to look for other types of circulating nucleic acids. In particular, the similarity between the placenta and a malignant neoplasm has led to the discovery of cell-free fetal DNA in the plasma and serum of pregnant women. Fetal DNA has been shown to be present in the plasma of almost all pregnant women, from the early first trimester onward, and to be present in increasing... 

The second main aspect of adhesion in medicine corresponds to the cellular level. A few examples will be given. In the development of a cancer, one major problem is that the patient is often only aware of the primary tumour when it has evolved sufficiently for metastases to have been released. These malignant cells are free to migrate within the body, often in the blood circulation, and create secondary tumours elsewhere in the body leading to a generalized iUness. Were we able to increase the adhesion of metastases to their source, many treatments of cancer could be limited to a specific area of the body. By contrast, consider a case where adhesion is undesirable. Heart disease is often related to the blocking of arteries by matter, in particular thrombi, or locally produced blood clots. 

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