Ilona Mucsi

Cancer prevention and therapy with kiwifruit in Chinese folklore medicine: A study of kiwifruit extracts

Kiwi gold fruits were extracted successively with hexane, acetone, methanol and 70% methanol, and further fractionated by silica gel and ODS column chromatographies for the assays of various biological activities. Five fractions H1, H2 (hexane extract), Al, A2 (acetone extract) and M2 (methanol extract) showed selective cytotoxic activity against human oral tumor cell lines, which was more sensitive than human gingival fibroblasts. More hydrophilic fractions [70M3, 70M4, 70M5] of 70% methanol extract displayed higher anti-HIV activity, radical generation and O2- scavenging activity. The antibacterial activity of 70% methanol extracts [70M0, 70M1, 70M2, 70M3, 70M4] was generally lower than that of more lipophilic fractions (hexane, acetone, methanol extracts), although each fraction did not show any specific antimicrobial action. All fractions were inactive against Helicobacter pylori. These results demonstrate that gold kiwifruit extracts contain valuable, various bioactive materials, which can be separated with each other.

Effect of ultraviolet irradiation and heating on the interferon-inducing capacity of human adenoviruses.

Summary Heating adenovirus types 8 and 12 for 2 to 3 min. at 56° simultaneously reduced both interferon-inducting capacity and infectivity. In contrast, virus inactivated by u.v.-irradiation effectively stimulated interferon production in chick cells. Chick cells infected with adenovirus type 12 and incubated at 25°, 35° or 40° produced about the same amount of interferon but the kinetics of interferon production differed, i.e. at the higher temperatures interferon formation commenced earlier. The possibility that the penton antigen may be responsible for interferon induction by human adenoviruses in chick cells is discussed.

Effect of treatment with certain flavonoids on Mengo virus-induced encephalitis in mice

SummaryAmong the four flavonoids tested quercetin and morin proved to be significantly effective against lethal Mengo virus-induced encephalitis in mice when the drugs were administered orally (p.o.). With subcutaneous (s.c.) administration all four drugs failed to prevent mortality in the infected mice. Quercetin produced maximum protective response in intraperitoneally (i.p.) or intranasally (i.nas.) infected mice when administered twice daily at doses of 20 mg/kg for a period of not less than four days. Single injections of the full daily dose of drug failed to prevent deaths in mice. Treatment must be begun at the time of, or prior to, virus inoculation. Delayed initiation of treatment was ineffective in preventing mortality.

Combination of benzo[a]phenothiazines with acyclovir against herpes simplex virus.

The combined antiviral effects of some benzo[a]phenothiazines and 9-[2-hydroxy(ethoxy)methyl]guanine (acycloguanosine, acyclovir, ACV) on the multiplication of herpes simplex virus type 2 (HSV-2) were studied using Vero cells. The antiviral effect of ACV on a wild strain of HSV-2 was enhanced in the presence of 5-oxo-5H-benzo[a]phenothiazine and 6-methyl-5-oxo-5H-benzo[a]phenothiazine in a yield reduction test. A mathematical formula was used to interpret the drug interaction and a synergistic effect was found with a combination of ACV and benzo[a]phenothiazines. The effect of simultaneous application of two benzo[a]phenothiazines on the multiplication of HSV-2 strain during serial passages was also investigated. The combinations of 5-oxo-5H-benzo[a]phenothiazine or 6-methyl-5-oxo-5H-benzo[a]phenothiazine with ACV at a low concentration using serial passages of a plaque-purified ACV sensitive HSV-2 strain, reduced the infective virus population. A similar effect was also found on the activity of other benzo[a]phenothiazine derivatives. When the two most effective derivatives of 5-oxo-5H-benzo[a]phenothiazine or 6-methyl-5-oxo-5H-benzo[a]phenothiazine were simultaneously used with ACV against a wild type HSV-2 strain during consecutive passages, the infective virus titres were decreased, but their effect was only moderate. These results suggest that a combination of some benzo[a]phenothiazines with ACV might enhance their antiviral activity probably by reduction of the mutagenic rate in the virus populations.

Inhibition of the adhesion of E. coli on cultured human epithelial cells in the presence of promethazine or imipramine.

The adhesion and multiplication of E. coli strain K12 with a derepressed synthesis of sex pili and of a nephropathogenic E. coli strain isolated from the urine of a patient with pyelonephritis, were demonstrated on the surface of cultured HEp-2 cells. The adhesion of the two E. coli strans was inhibited in the presence of 0.5-5.0 micrograms/ml promethazine or imipramine, but the multiplication of the bacteria on the monolayers was not decreased significantly in the presence of the two drugs. A scanning electronmicroscopic technique was developed to study bacterial adhesion and colony formation on epithelial cells.

Rescue of Heat-inactivated Adenovirus Types 1 and 6 by Ultraviolet-irradiated Adenovirus Type 8

Summary Heating human adenovirus types 1 and 6 at 56° reduced infectivity very rapidly. A treatment for 10 to 15 min. usually completely destroyed the infectivity. However, the rescue of heated virus occurred when HEp-2 cells were inoculated simultaneously with heat-inactivated type 1 or 6 and u.v.-irradiated type 8. Rescue was dependent upon the length of heat treatment, as viruses heated at 56° for more than 20 min. could not be rescued. On the other hand, the rescue of heat-inactivated type 6 was related to the u.v. dose employed, i.e. type 8 unirradiated or irradiated for 20 min. was not suitable for rescue. The possible mechanism of rescue observed with heat-inactivated adenovirus types 1 and 6 by u.v.-irradiated type 8 is discussed.

The Role of Stroma in Tumour-Host Co-Existence: Some Perspectives in Stroma-Targeted Therapy of Cancer

Cancer grows at the expense of the host as a parasite or superparasite following the second law of thermodynamics (conservation of energy). When the cancer cell progresses via replication to the special state called “spheroid”, a new phase begins with its intimiate interaction and development of responses from the stroma which together assist in the formation of a full blown cancer. Among the processes involved are the development of blood vessels and lymphatic channels which are essential for maintenance and further growth of the cancer mass. In this way the condition of “parasitism” is completed with simultaneous suppression of the immune response of the host to the histoincompatability of the tumor mass. Stroma/parenchyma promotes cancer invasion by feeding cancer cells and inducing immune tolerance. The dynamic changes in composition of stroma and biological consequences as feeder of cancer cells and immune tolerance can give a perspective for rational drug design in anti-stromal therapy. There are differences between normal and cancer cells at subcellular level such as compartmentalzation and structure of cytoskeleton and energy distribution (that is low generally, but locally high in normal cells). In cancer cannibalism of normal cells, the growing cancer mass is a factor for progression and invasion. Cancer cells have been shown to kill normal cells and the products of cell death used for progression of growth of the cancer cell. Serum and growth factors produced by tumor stroma also provide the needed nutrients and conditions for further tumor growth. Cancer cannot feed off other cancer cells and therefore grow poorly. Probably, although not yet proven, the inability of cancer to “parasitise” other cancer cell types is probably due to some kind of competition or interference. The tumor is in charge of its own development due to its induction proteinases, lipid mobilization factors and angiogenetic factors as well as its ability to negate immune responses of the host response to what is in essence a foreign body. In our review co-existence of normal and cancer cells in tumor with the growth promoting factors, and the immune tolerance mediating factors produced in the stromal and cancer cells/tissues will be discussed with perspective of stroma targeted therapy.