Skeletal Muscle Tumors

Vimentin +, sr Actin +, Desmin +, Myosin +, Myoglobin +/—, MyoDl +/—, GFAP —/+ Vimentin +, Desmin +, Actin +, Myoglobin +, Myosin +/—, Myotilin +/—, SlOO — 

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Molenaar WM, Muntinghe FL. Expression of neural adhesion molecules and neurofilament protein isofotms in skeletal muscle tumors. Hum Pathol. 1998 29 1290-1293. 

In humans, also, preferential sites exist for the formation of metastasis from various primary tumors [reviewed in Zetter (Zl)]. Thus, bone is a preferred site for metastasis from primary malignancies in breast, prostate, and kidney, while liver is a frequent metastatic site for tumors originating in the colon. Different types of leukemias vary widely in their ability to spread to liver, lymph, bone, and spleen. Some organs, however, are rarely colonized by metastatic growth. These resistant sites include skeletal muscle, heart, and skin. 

The major problem associated with plasmid based gene delivery to skeletal muscle is the relatively low efficiency of transfection. Recent developments have demonstrated improved delivery associated with the application of an electrical field to the muscle after injection of the plasmid DNA (109). It is clear that the application of naked DNA close to the site of pathology and away from degradative elements such as plasma is thus a viable strategy for gene delivery. However, this method is ineffective if DNA dosing to anatomically inaccessible sites (e.g., solid tumors in organs) is desired. 

Kawase, A., Nomura, T., Yasuda, K., Kobayashi, N., Hashida, M., Takakura, Y. (2003). Disposition and gene expression characteristics in solid tumors and skeletal muscle after direct injection of naked plasmid DNA in mice. J. Pharm. Sci., 92(6), 1295-1304. 

Transfection efficacy of naked DNA can be increased by physical methods such as electroporation and sonication. Electroporation employs electric pulses to punch holes in the cell membrane, usually smaller than 10 nm but larger than oligonucleotides. With the use of electroporation, DNA was delivered into the cytosol of cells by diffusion. Since its introduction in 1982, in vivo transfection has been achieved in skeletal muscle, fiver, skin, tumors, testis, and the kidney. Tsujie et al. (2001) developed a method to target glomeruli using electroporation in vivo wherein injection of plasmid DNA via the renal artery was followed by application of electric fields. The kidney was electroporated by sandwiching the organ... 

Figure 6. Whole body nitrogen balance and cellular hydration of skeletal muscle. Data were obtained from humans. A healthy subjects (n = 17) B liver tumors (n = 5), C polytrauma day 2 and D day 9 after trauma (n = 11) E acute necrotizing pancreatitis (n = 6) F burn patients (n = 4). (From Haussinger et. al., 1993.)...

EAG has a rather restricted distribution in healthy tissues it expresses nearly exclusively in brain, slightly in placenta and transiently in skeletal muscle (Occhiodoro et al. 1998 Pardo et al. 1999). In contrast to its restricted distribution in normal tissues, expression of EAG has been found in several human somatic cancer cell lines including HeLa cervix carcinoma, MCF-7 and SHSY-5Y neuroblastoma derived from breast tumor, melanoma IGR1, rhabdomyosarcoma, etc. (Meyer 1998, 1999 Crociani 2003). Most notably, EAG mRNA expression was found in 100% of the human cervical cancer sam-... 

Chronic excessive nutrient intake leads to the deposition of fat, in not only its normal storage site, which is the adipose tissue, but also in liver and skeletal muscle. Nutrient excess also triggers an inflammatory response, with the release of inflammatory cytokines [tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), and CRP]. These inflammatory mediators, along with the intracellular accumulation of lipid metabolites, lead to impaired insulin receptor signaling and defective metabolism in skeletal muscle and liver (37, 38). Nutrient excess also damages cells by generating reactive oxygen species, which results... 

Muscular system disorders related to the immune system include myasthenia gravis (MG) and tumors. MG is characterized by weak and easily fatigued skeletal muscles, one of the symptoms of which is droopy eyelids. 

MG is caused by antibodies that a person makes against their own Ach receptors hence, MG is an autoimmune disease. The antibodies disturb normal Ach stimulation to contract skeletal muscles. Failure of the immune system to destroy cancerous cells in muscle can result in muscle tumors. Benign muscle tumors are called myomas while malignant muscle tumors are called myosarcomas. 

Emetine, once the drug of choice for the treatment of amebiasis, despite marked cardiotoxicity, has largely been replaced by metronidazole and related compounds for this indication. Large doses of emetine can damage the heart, hver, kidneys, intestinal tract, and skeletal muscle. Allergic reactions and tumor-inducing effects have not been described. Dehydroemetine is a httle less toxic but also less effective than emetine its adverse effects are similar (SED-11, 594). 

Whenever insulin levels in the blood are chronically elevated as occurs, for example, in patients with insulin-secreting pancreatic tumors or in patients inadvertently given excessive quantities of exogenous insulin, the transport of glucose from the blood into tissues such as skeletal muscle... 

When injected into skeletal muscle or solid tumor tissue, plasmid DNA undergoes degradation as well as absorption into the blood circulation.16 A fraction of the plasmid DNA is absorbed from the lymphatic system after injection into these tissues. Plasmid DNA and its degraded products exhibit distribution profiles similar to that obtained with intravenous plasmid DNA. 

The electroporation-mediated in vivo gene transfer had been successfully used for hepatic parenchyma (70, 71), hepatocellular carcinoma (72), skin (73,74), skeletal muscle (69, 75,761, mouse testes (77), melanoma (65), human primary myoblast (78), glomeruli (79), brain (80), human primary hematopoietic stem cells (81), human esophageal tumor (82), and rat skeletal muscle for correcting anemia of renal failure (83). 

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