Periappendiceal abscess mimicking appendiceal cancer.

Appendiceal cancer was strongly suspected in this case because of its unique colonoscopic, radiologic, and intraoperative presentation. Hence, laparoscopic enbloc right hemicolectomy and peritonectomy were performed. The diagnosis of periappendiceal abscess was confirmed later after the operation. Appendiceal disease is hard to differentiate because of the wide spectrum of differential diagnosis. So, when there is a strong suspicion of appendiceal cancer, laparoscopic right colectomy, which is minimally invasive and potentially curative can be the treatment of choice.

Effect of analogs with modified prenyl side chains on growth of serum deficient HL60 cells.

This study was organized by Professor Karl Folkers with the objective of finding derivatives of coenzyme Q which could be more effectively absorbed and would give better biomedical effects. In this series all the compounds are 2,3 dimethoxy, 5 methyl p benzoquinone with modified side chains in the 6 position. The modifications are primarily changes in chain length, unsaturation, methyl groups and addition of terminal phenyl groups. The test system evaluates the growth of serum deficient HL60, 3T3 and HeLa cells in the presence of coenzyme Q10 or coenzyme Q analogs. Short chain coenzyme Q homologues such as coenzyme Q2 give poor growth but compounds with saturated short aliphatic side chains from C10 to C18 produce good growth. Introduction of a single double bond at the 2' or 8' position in the aliphatic chain retains growth stimulation at low concentration but introduces inhibition at higher concentration. Introduction of a 3' methyl group in addition to the 2' enyl site in the side chain decreases the growth response and maintains inhibition. Addition of a terminal phenyl group to the side chain from C5 to C10 can produce analogs which give strong stimulation or strong inhibition of growth. The action of the analogs is in addition to the natural coenzyme Q in the cell and is not based on restoration of activity after depletion of normal coenzyme Q. The effects may be based on any of the sites in the cell where coenzyme Q functions. For example, coenzyme Q2 is known to decrease mitochondrial membrane potential whereas the analog with a 10C aliphatic side chain increases potential. Both of these compounds stimulate plasma membrane electron transport. Inhibition of apoptosis by coenzyme Q may also increase net cell proliferation and the 10C analog inhibits the permeability transition pore.

Association of cyclooxygenase-2 expression with prognosis of stage T1 grade 3 bladder cancer.

OBJECTIVES: To determine whether the expression of cyclooxygenase-2 (COX-2) has prognostic significance in Stage T1G3 transitional cell carcinoma of the bladder, the most unfavorable subgroup in terms of recurrence and disease progression. METHODS: Thirty-seven consecutive patients with initial T1G3 transitional cell carcinoma, who had undergone complete transurethral resection, followed by 6 weeks of intravesical instillation of bacille Calmette-Guérin (BCG), and with at least 1 year of follow-up, were enrolled in the study. Paraffin-embedded cancer tissue samples were immunohistochemically stained for COX-2, and possible correlations with clinicopathologic features, such as age, shape and multiplicity of tumor, recurrence, and progression were examined. RESULTS: The median follow-up was 27 months (range 12 to 67). Sixteen patients (43.2%) experienced recurrence and 6 (16.2%) had progression defined as muscle invasion. Of 37 specimens, 16 (43.2%) stained positive for COX-2, defined as 5% or greater of positively stained cancer cells. COX-2 expression was statistically significant in predicting both recurrence (P = 0.0493) and disease progression (P = 0.0272). Patient age and the shape and multiplicity of tumors were not significantly predictive of recurrence or progression. CONCLUSIONS: In a pathologically homogeneous group of T1G3 transitional cell carcinoma of the bladder, the expression of COX-2 correlated with recurrence and progression. Thus, patients with COX-2 positive superficial bladder cancer may need to be followed up more vigorously. Additional studies on the mechanistic implications of COX-2 with respect to recurrence and progression and the possible application of a COX-2 inhibitor to prevent recurrence and progression of superficial bladder cancer are warranted.

Cytokine inhibition of transplasma membrane election transport.

Two cytokines, interferon gamma and tumor necrosis factor alpha, which can inhibit cell proliferation or induce cell death, have been found to inhibit transplasma membrane electron transport. The concentrations required for inhibition of election transport are similar to concentrations effective in inhibition of cell growth. Since inhibition of election transport has been related to apoptosis and modification of election transport can cause oxygen radical formation, the changes in electron transport induced by the cytokines can contribute to known mechanisms of cytokine cytotoxicity.

Bombesin stimulates transplasma-membrane electron transport by Swiss 3T3 cells.

Bombesin, a mitogenic neuropeptide, stimulates transplasmalemma reduction of diferric transferrin or ferricyanide by Swiss 3T3 cells. The stimulation of diferric transferrin reduction occurs in the range of bombesin concentrations that stimulate proliferation of Swiss 3T3 cells. Diferric transferrin reduction by the 3T3 cells is accompanied by increased proton release from the cells and bombesin increases the differic transferrin-stimulated proton release twofold. Insulin increases the diferric transferrin reductase response and increases growth stimulation with bombesin. The effect of bombesin on the transmembrane electron transport is a new aspect of its effect on the plasma membrane in addition to increase in phosphatidylinositol turnover and protein kinase c activation. The electron transport can provide an independent mechanism of activation of the Na+/H+ exchange or it can change the redox state of pyridine nucleotide in the cytoplasm.

Coenzyme Q10, plasma membrane oxidase and growth control.

The plasma membrane of eukaryotic cells contains an NADH oxidase which can transfer electrons across the membrane. This oxidase is controlled by hormones, growth factors and other ligands which bind to receptors in the plasma membrane. Oncogenes also affect activity of the oxidase. Natural serum components such as diferric transferrin and ceruloplasmin which stimulate proliferation also stimulate membrane oxidase activity. Additional growth factors can be required to complement the proliferative effect. Electron transport across the plasma membrane can be measured by the reduction of impermeable electron acceptors, such as ferricyanide, which also stimulate cell growth. The oxidants activate growth-related signals such as cytosolic alkalinization and calcium mobilization. Antiproliferative agents such as adriamycin and retinoic acid inhibit the plasma membrane electron transport. Flavin, Coenzyme Q and an iron chelate on the cell surface are apparent electron carriers for the transmembrane electron transport. Coenzyme Q10 stimulates cell growth, and Coenzyme Q analogs such as capsaicin and chloroquine reversibly inhibit both growth and transmembrane electron transport. Addition of iron salts to the depleted cells restores activity and growth. The ligand-activated oxidase in the plasma membrane introduces a new basis for control of signal transduction in cells. The redox state of the quinone in the oxidase is proposed to control tyrosine kinase either by generation of H2O2 or redox-induced conformational change.

The essential functions of coenzyme Q.

The essential role of coenzyme Q in biological energy transduction is well established. Coenzyme Q is a unique carrier for two-electron transfer within the lipid phase of the mitochondrial membrane. The function is essential for proton-based energy coupling. The sites of entry and exit of electrons into the quinone are at specific quinone-binding sites which are constructed to allow only two-electron transfer and thus prevent damaging free radical formation by direct reaction of oxygen with the semiquinone. Failure of proper function with diminished energy supply can be related to insufficient quinone, modification of lipid fluidity, or lipid protein interaction and damage or poisoning in binding sites. Supplementation with coenzyme Q can act by reversal of deficiency or decreased mobility, or by overcoming binding site modification. Coenzyme Q has also been shown to increase antioxidant protection in membranes. New sites for coenzyme Q function in Golgi and plasma membrane show evidence for a role in growth control and secretion-related membrane flow.

Requirement for coenzyme Q in plasma membrane electron transport.

Coenzyme Q is required in the electron transport system of rat hepatocyte and human erythrocyte plasma membranes. Extraction of coenzyme Q from the membrane decreases NADH dehydrogenase and NADH:oxygen oxidoreductase activity. Addition of coenzyme Q to the extracted membrane restores the activity. Partial restoration of activity is also found with alpha-tocopherylquinone, but not with vitamin K1. Analogs of coenzyme Q inhibit NADH dehydrogenase and oxidase activity and the inhibition is reversed by added coenzyme Q. Ferricyanide reduction by transmembrane electron transport from HeLa cells is inhibited by coenzyme Q analogs and restored with added coenzyme Q10. Reduction of external ferricyanide and diferric transferrin by HeLa cells is accompanied by proton release from the cells. Inhibition of the reduction by coenzyme Q analogs also inhibits the proton release, and coenzyme Q10 restores the proton release activity. Trans-plasma membrane electron transport stimulates growth of serum-deficient cells, and added coenzyme Q10 increases growth of HeLa (human adenocarcinoma) and BALB/3T3 (mouse fibroblast) cells. The evidence is consistent with a function for coenzyme Q in a trans-plasma membrane electron transport system which influences cell growth.

Stimulation of serum-free cell proliferation by coenzyme Q.

Coenzyme Q added to culture media stimulates the growth of HeLa and Balb/3T3 cells in serum free conditions. The stimulation by coenzyme Q is additive to the stimulation by ferricyanide, an impermeable electron acceptor for the transplasma membrane electron transport. alpha Tocopherylquinone can also stimulate cell growth, but vitamin K1 is inactive or inhibitory. The response to coenzyme Q and ferricyanide is enhanced with insulin. A contribution to plasma membrane NADH oxidation or modification of the membrane quinone redox balance can be a basis for the growth stimulation.

A growth factor- and hormone-stimulated NADH oxidase from rat liver plasma membrane.

NADH oxidase activity (electron transfer from NADH to molecular oxygen) of plasma membranes purified from rat liver was characterized by a cyanide-insensitive rate of 1 to 5 nmol/min per mg protein. The activity was stimulated by growth factors (diferric transferrin and epidermal growth factor) and hormones (insulin and pituitary extract) 2- to 3-fold. In contrast, NADH oxidase was inhibited up to 80% by several agents known to inhibit growth or induce differentiation (retinoic acid, calcitriol, and the monosialoganglioside, GM3). The growth factor-responsive NADH oxidase of isolated plasma membranes was not inhibited by common inhibitors of oxidoreductases of endoplasmic reticulum or mitochondria. As well, NADH oxidase of the plasma membrane was stimulated by concentrations of detergents which strongly inhibited mitochondrial NADH oxidases and by lysolipids or fatty acids. Growth factor-responsive NADH oxidase, however, was inhibited greater than 90% by chloroquine and quinone analogues. Addition of coenzyme Q10 stimulated the activity and partially reversed the analogue inhibition. The pH optimum for NADH oxidase was 7.0 both in the absence and presence of growth factors. The Km for NADH was 5 microM and was increased in the presence of growth factors. The stoichiometry of the electron transfer reaction from NADH to oxygen was 2 to 1, indicating a 2 electron transfer. NADH oxidase was separated from NADH-ferricyanide reductase, also present at the plasma membrane, by ion exchange chromatography. Taken together, the evidence suggests that NADH oxidase of the plasma membrane is a unique oxidoreductase and may be important to the regulation of cell growth.