Cancer Autonomous

The chromatid separation process has also remained mysterious. It is an autonomous process that does not direcdy depend on the mitotic spindle (Wilson 1925, Mazia 1961). This is most vividly seen in cells whose spindles have been destroyed by spindle poisons such as colchicine. In many organisms, in particular in plant cells, the cell cycle delay induced by colchicine is only transient and chromatids eventually split apart in the complete absence of a mitotic spindle (Mole-Bajer 1958, Rieder Palazzo 1992) (Fig. 2). Mitosis in the presence of colchicine or colcemid (known as c-mitosis) leads to the production of daughter cells with twice the normal complement of chromosomes. This process is routinely used for manipulating plant genomes and may contribute to the therapeutic effects of taxol in treating breast cancer. 

Antibodies cause calcium channel dysfunction in Lambert-Eaton syndrome. Some patients with cancer, especially small-cell carcinoma of the lung, develop a syndrome of weakness associated with autonomic dysfunction as part... 

We now have a greater appreciation of the multiple hallmarks of cancer (4) and understand that tumors are not simply autonomous factories generating hyper-proliferating cells. Indeed, they depend upon many additional properties, several of which are dependent on the host and which may offer new vulnerabilities for therapeutic... 

Given orally at normal therapeutic doses BDZs have little effect on cardiovascular, respiratory or autonomic function. Respiratory depression and reduced systolic blood pressure may occur but this is seen principally with intravenous administration or overdose. Leucopenia and eosinophilia are rare. There was a suggestion in the early 1980s of increased risk of breast cancer but a subsequent large case-control study refuted this. 

Cancer is the unrestrained, malignant proliferation of a somatic cell producing a neoplasm or tumor defined as a heritably altered relatively autonomous growth. So its characteristics are (i) heritable nature and (11) relative autonomy. 

Hojo, M., Morimoto, T., Maluccio, M., Asano, T., Morimoto, K. el al. (1999). Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature397, 530-534. 

PEM is one of the most frequent cancer-associated syndromes. This complex disorder usually affects several areas of the CNS. Cerebellar and brain stem disorders, as well as limbic encephalitis, are the most common clinical presentations of PEM [31, 32], Focal involvement of the sensorimotor cortex has been described in a few cases [33], and PEM may manifest as epileptic seizures or epilepsia partialis continua [33, 34], or as extrapyramidal symptoms [35], Two-thirds of the patients are affected in both the CNS and the peripheral nervous system. The predominant feature in more than half of these is SN [32, 36], hence the commonly used term is PEM/SN. Autonomic dysfunction is common in PEM/SN patients [36], often presenting as gastrointestinal dysmotility [37]. 

Paraneoplastic autonomic neuropathy is primarily seen with SCLC [103]. Lymphoma, non-small cell lung cancer, and ovarian cancer are also associated with autonomic disturbances [104]. Autonomic dysfunction affects 23-30% of Hu antibody positive patients [36, 98] and is the predominant symptom at presentation in up to 9% of the patients [90]. The onset of symptoms is usually subacute. A prominent clinical manifestation in patients with paraneoplastic autonomic neuropathy is gastrointestinal dysmotility and intestinal pseudo-obstruction, which can occur as part of the PEM/SN syndrome or as the sole symptom of Hu antibody related PNS. Ortostatic hypotension and erectile dysfunction are other common features [37, 105, 106], Autonomic neuropathy is also commonly associated with the CRMP-5 antibody and have been detected in more than 30% of CRMP-5 antibody positive patients [30], Inflammation in autonomic ganglia and infiltration of B and T cells have been demonstrated at autopsy [107], and Hu antibodies have been shown to induce neuronal apoptosis in cultured myenteric neurons [105],... 

Ashraf S, Crowe R, Loizidou MC, Turmaine M, Taylor I, Burnstock G. The absence of autonomic perivascular nerves in human colorectal liver metastases. Br J Cancer 1996 ... 

H17. Hofer, D. R., Sherwood, E. R., Bromberg, W. D., Mendelsohn, J., Lee, C., and Kozlowski, J. M., Autonomous growth of androgen-independent human prostatic carcinoma cells Role of transforming growth factor alpha. Cancer Res. 51, 2780-2785 (1991). 

Hojo M, Morimoto T, Maluccio M, Asano T, Morimoto K, Lagman M, et al Cyclosporin induces cancer progression by a cell-autonomous mechanism. Nature 1999 397 530-534. 

Viniegra M, Marchetti M, Losso M, Navigante A, Litovska S, Senderowicz A, Borghi L, Lebron J, Pujato D, Marrero H, et al. Cardiovascular autonomic function in anthracycline-treated breast cancer patients. Cancer Chemother Pharmacol 1990 26(3) 227-31. 

Encephalopathy, peripheral neuropathy, cerebellar syndromes, autonomic neuropathy, and cranial nerve toxicity represent the range of neurological complications associated with cancer chemotherapy. Dose, route of administration, age of the patient, hepatic and renal function, prior and/or concomitant use of other neurotoxic drugs, and the concurrent use of cranial or CNS radiotherapy can each influence the incidence rate and severity of neurologic symptoms associated with selected chemotherapy drugs. 

As discussed in Chapter 16, the question of whether or not athermal levels of microwave fields are toxic is a controversial one. One study, however, found that such microwaves act synergistically with chemical cancer promoters and lead to autonomous cell growth. 711 This effect has been demonstrated in vitro using the combination of cancer promoting phorbol esters co-applied with nonionizing electromagnetic fields. The author of the study hypothesizes that the mechanism of the combined radiation/ chemical effect involves the disruption of normal intercellular communication through gap junctions. 

Andreescu, S. Sadik, O. A. McGee, D. W., Autonomous multielectrode system for monitoring the interactions of isoflavonoids with lung cancer cells, Anal. Chem. 2004, 76, 2321-2330... 

Important features of cancer cells are enhanced genetic instability, dysregulated and autonomous cell proliferation, increased cell survival, and the ability to survive in a foreign cellular environment which exposes the cell to various stresses. Overall, these properties provide an advantage for the cancer cell. 

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