Implications and Efficacy of Aromatase Inhibitors in Combination and Monotherapy for the Treatment of Lung Cancer.

BACKGROUND: Lung tumors express high levels of aromatase enzyme compared to surrounding normal tissue. Inhibition of aromatase has emerged as a recent therapeutic approach for the treatment of breast cancer. However, the role of aromatase inhibition in lung cancer treatment requires further investigation. METHODS: The anti-proliferative effects of aromatase inhibitors were evaluated by MTT assay. Cell migration was assessed using a wound healing assay. The mechanism of cell death was determined using the annexin VFITC/ propidium iodide staining flow cytometry method. The soft agar colony formation assay evaluated cells' capability to form colonies. RESULT: Exemestane and curcumin significantly inhibited the growth of lung cancer cell lines in a dose- and timedependent manner. The IC50 values after 48 hours of treatment with exemestane were 176, 180, and 120 µM in A549, H661, and H1299, respectively. Curcumin IC50 values after 48 hours were 80, 43, and 68 µM in A549, H661, and H1299, respectively. The combined treatment of exemestane or curcumin with cisplatin, raloxifene, and celecoxib resulted in a synergistic effect in the A549 lung cell line with a combination index of less than 1, suggesting synergism. Exemestane resulted in approximately 96% inhibition of wound closure at 100 µM, while curcumin resulted in approximately 63% inhibition of wound closure at 50 µM. Exemestane and curcumin inhibited the formation of cell colonies by reducing the number and size of formed colonies of A549, H661, and H1299 cell lines in a concentration dependent manner. Exemestane and curcumin had significantly induced apoptosis in A549 cells compared to control of untreated cells. CONCLUSION: Aromatase inhibition by exemestane or curcumin had significantly inhibited the growth of lung cancer cell lines, synergized with cisplatin, raloxifene, and celecoxib, suppressed lung cancer cell migratory potential, induced apoptosis, and reduced colony formation of lung cancer cells.

Pharmacological interventions for the treatment of neonatal jaundice.

In the neonate, hyperbilirubinaemia is usually due to a combination of an increased bilirubin load and decreased bilirubin elimination. Despite an understanding of the enzymatic pathways leading to bilirubin production and elimination, very few pharmacological interventions to prevent hyperbilirubinaemia are utilized and the mainstay of treatment remains phototherapy. Previously studied pharmacological agents such as D-penicillamine, phenobarbital and clofibrate may yet prove useful. Recent clinical trials using metalloporphyrins to inhibit heme catabolism and bilirubin production provides a novel pharmacological intervention for the treatment of neonatal jaundice. The safety and efficacy of these therapies will need to be confirmed prior to widespread use.

Sulfated polysaccharides (chondroitin sulfate and carrageenan) plus glucosamine sulfate are potent inhibitors of HIV.

AIDS: Chondroitin sulfate, a fusion inhibitor found in human milk, appears to work by blocking the ability of a virus, such as HIV, to infect a cell. There are questions about whether cow or goat milk can offer the same fusion-inhibiting benefits. One sulfated monosaccharide, glucosamine 6-sulfate, appears to have significant anti-HIV activity. Carrageenan, a seaweed derivative, shows promise as a vaginal microbicide, and should be tested further to determine its effectiveness against HIV transmission.^ieng

Superiority of oral agar and phototherapy combination in the treatment of neonatal hyperbilirubinemia.

OBJECTIVE: To determine the value of oral agar in the treatment of neonatal hyperbilirubinemia and to compare it with two other treatment modalities: phototherapy alone and phototherapy plus oral agar. METHODS: Two hundred eight jaundiced full-term newborns were divided into four groups. They were given either phototherapy alone, phototherapy plus oral agar, oral agar alone, or no treatment (control group). The changes in the serum bilirubin values were determined and the results were compared statistically, mainly using analysis of variance. RESULTS: In all three therapy groups, the time required to reduce the bilirubin level to either 15 mg/dL or to 10 mg/dL was significantly shorter than that required by the control group. Although oral agar was found to be as effective as phototherapy, the most significant decrease in bilirubin level was in the combination group. CONCLUSIONS: The efficacy of phototherapy in decreasing the serum bilirubin level in neonatal hyperbilirubinemia can be augmented with the use of oral agar. Oral agar can also be used as a single agent for the treatment of neonatal hyperbilirubinemia, since it is as effective as phototherapy.

[Antisteatotic effects of four kinds of dietary fibers in rats fed on high cholesterol diet: a preliminary morphometric analysis].

The hypolipidaemic and antisteatotic effects of the Konnyaku Powder (KP) have been reported before. In order to evaluate further the antisteatotic role played by KP, the effects of KP on the levels of liver lipid and on the hepatic histopathology and morphometry in comparison with those of pectin, algin and agar were studied. Sixty Wistar strain rats were divided into 6 groups: a normal diet group, a high cholesterol diet group (HC), and 4 test groups, in which the animals were fed on a diet similar to that of the high cholesterol diet group with addition of KP, pectin, algin or agar at a dosage of 5%, respectively. All the animals were killed at the end of the diet treatment for 9 weeks. The results showed that relative liver weights were lower in four experimental groups than in the HC group. The levels of total and free cholesterol, and triglyceride in the liver were lower in KP group than in HC group and in the other three experimental groups. Hepatic histopathology and morphometric examination indicated that antisteatotic effects of KP appeared to be much more significant than those of the other fibers.

Chemical and physical properties of a hydrogel wound dressing.

Geliperm hydrogel provides optimal physiological conditions for wound healing. The material is composed of two interlaced networks, one of polyacrylamide and one of agar, and contains about 96% firmly bound water. It is supplied in smooth, elastic, transparent sheets which are impermeable to bacteria but permeable to gases, salts, metabolites and proteins. Geliperm is nontoxic and has no irritative properties. Mechanical properties, water retention and diffusion of dyes and proteins are reported. Bacterial size should preclude penetration of the gel. The hydrogel in granular form represents a coherent material which could be used in deep fissured wounds and for the treatment of injuries with a large amount of exudation and contamination.

Randomized controlled trial of Syn-Ergel and an active placebo in the treatment of heartburn of pregnancy.

A randomized controlled trial was performed to study the efficacy of Syn-Ergel with an active placebo in the treatment of heartburn of pregnancy in ninety-two patients completing 7 days of therapy. Syn-Ergel was significantly better (p less than 0.001) in all groups of pre-treatment pain severity in relieving the symptoms, and had a longer duration of action, than the active placebo. Complete relief of pain was achieved in 79.5% of Syn-Ergel treatments with a further 10% of treatments resulting in marked easing of discomfort at 1 hour following administration. The corresponding figures for the 'active placebo' were 56% and 20%. The combination of an antacid and a protective mucosal coating agent would appear to be a useful approach in the treatment of heartburn of pregnacy.

Agar ingestion combined with phototherapy in jaundiced newborn infants.

49 jaundiced, nonimmunized newborn infants with a birth weight of more than 2,000 g were given phototherapy with white light for more than 36 h. The average period of treatment was 61 h. 24 infants received 250 mg agar at the beginning of each meal at 3-hour intervals during phototherapy. 25 infants received phototherapy only. Serum bilirubin levels were decreased similarly in both groups. It is concluded that ingestion of agar does not supplement the effect of phototherapy.

Comparison of treatments for congenital nonobstructive nonhaemolytic hyperbilirubinaemia.

A patient with Crigler-Najjar disease has survived with the help of phototherapy to the age of 2 years without neurological damage. Because long periods of phototherapy are a threat to normal development, a search was made for supplementary treatments. Cholestyramine and a high fat diet were effective, and possibly also aspartic acid. Maintenance therapy with cholestyramine allowed the amount of phototherapy given to be reduced.

Agar in the management of hyperbilirubinaemia in the premature baby.

Eighty low birthweight infants (1500 to 2500 g) were randomly assigned to a group given oral agar and a control group. The study was first performed in 24 agar-fed babies and 24 control babies. The treated infants received a daily total amount of 600 mg/kg of agar beginning at 12 hours of age, for 7 days. In the later stage of the trial, 16 agar-fed babies and 16 control babies were investigated. The total daily amount of agar was raised to 700 mg/kg, beginning at 6 hours of age for 7 days. No complications were observed with the administration of agar. Serum bilirubin levels were not significantly lower in the agar-fed infants. We conclude that agar supplemented feeding is not indicated in the management of hyperbilirubinaemia in low birthweight newborn infants.