Infectious bursal disease virus (IBDV) was inactivated by two different chemicals--formaldehyde and binary ethylenimine (BEI). Formaldehyde was used at 0.1% and 0.2%, while BEI was used at concentrations of 0.001 and 0.002 mol/L. These four vaccines were tested for their efficiency in generating humoral immune response in different groups of broiler chicks. Both BEI-inactivated vaccines gave relatively higher antibody titers and were almost twice as efficient as formaldehyde-inactivated ones.
Animals ; Antibodies, Viral ; blood ; Aziridines ; pharmacology ; Chickens ; Formaldehyde ; pharmacology ; Infectious bursal disease virus ; immunology ; Vaccination ; Vaccines, Inactivated ; immunology ; Viral Vaccines ; immunology

AIMTo examine the effect of inducible nitric oxide synthase (iNOS) on tumour cells chemosensitivity to mitomycin C (MMC) analogue 5-aziridinyl-3-hydroxyl-1-methylindole-4,7-dione (629) in vitro, and elucidate the possible role of iNOS in the metabolism of 629.

METHODSHuman sarcoma cells (HT1080) and its iNOS gene transfected clones (iNOS9, iNOS12) were exposed to 629 at concentrations of 1 nmol x L(-1) - 100 micromol x L(-1). 3-[4, 5-Dimethylthiazol-2-yl] -2,5-diphenyltetrazolium bromide (MTT) assay, agarose electrophoresis and flow cytometric analysis were used to determine cell sensitivity, deoxyribonucleic acid (DNA) damage and the change of cell cycle in above process, respectively. All experiments were performed both in air and under hypoxia parallelly.

RESULTS629 was more toxic than MMC, and enhanced cytotoxicity under hypoxia, which resulted in cell necrosis. Sixteen hours after treated with 629, HT1080 cells and related iNOS-transfected clone cells were obviously blocked in G2/M phase.

CONCLUSIONiNOS plays dual roles in 629 metabolism, enhancing or decreasing the cytoxicity of 629 depending on the intracellular oxygen pressure P(O2), which caused higher cytotoxicity to hypoxia cells of 629 with the increasing of iNOS activity.

Antibiotics, Antineoplastic ; pharmacology ; Aziridines ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; DNA Damage ; Fibrosarcoma ; metabolism ; pathology ; Flow Cytometry ; Humans ; Indoles ; pharmacology ; Mitomycin ; chemistry ; pharmacology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Transfection

Hypoxia, a state of low oxygen, is a common feature of solid tumors and is associated with disease progression as well as resistance to radiotherapy and certain chemotherapeutic drugs. Hypoxic regions in tumors, therefore, represent attractive targets for cancer therapy. To date, five distinct classes of bioreactive prodrugs have been developed to target hypoxic cells in solid tumors. These hypoxia-activated prodrugs, including nitro compounds, N-oxides, quinones, and metal complexes, generally share a common mechanism of activation whereby they are reduced by intracellular oxidoreductases in an oxygen-sensitive manner to form cytotoxins. Several examples including PR-104, TH-302, and EO9 are currently undergoing phase II and phase III clinical evaluation. In this review, we discuss the nature of tumor hypoxia as a therapeutic target, focusing on the development of bioreductive prodrugs. We also describe the current knowledge of how each prodrug class is activated and detail the clinical progress of leading examples.
Anthraquinones ; chemistry ; pharmacology ; Antineoplastic Agents ; chemistry ; pharmacology ; Aziridines ; chemistry ; pharmacology ; Cell Hypoxia ; drug effects ; Humans ; Indolequinones ; chemistry ; pharmacology ; Molecular Structure ; NAD(P)H Dehydrogenase (Quinone) ; chemistry ; pharmacology ; Neoplasms ; drug therapy ; pathology ; Nitrogen Mustard Compounds ; chemistry ; pharmacology ; Nitroimidazoles ; chemistry ; pharmacology ; Phosphoramide Mustards ; chemistry ; pharmacology ; Prodrugs ; chemistry ; pharmacology ; Triazines ; chemistry ; pharmacology

This study is to evaluate the cytotoxicity of mitomycin C (MMC) and its analogue 5-(aziridin-1-yl)-3-hydroxymethyl-1-methylindole-4,7-dione (629) as well as the effect of transfection of constitutive androstane receptor (CAR) on their biological effects. HepG2 cells were transfected with the plasmids mCAR1/pCR3 mediated by liposome. Vector pCR3 was used as control. Transfected cells were screened by G418 resistance and limiting dilution. The expressions of plasmid mCAR1/pCR3 and CYP2B6 mRNA were detected by RT-PCR; Cytotoxicities of MMC and 629 in vitro were evaluated in g2car cells and HepG2 cells by MTT method under anaerobic and aerobic conditions. mRNA expression of CAR and CYP2B6 can not be detected in HepG2 cells and HepG2/pCR3 cells but can in g2car cells. It is shown that plasmid mCAR1/pCR3 was transfected into g2car cells successfully and target CYP2B6 was transactivated by CAR. To compare with aerobic and anaerobic, the cytotoxicities of MMC and 629 to HepG2 cells and g2car cells had significantly enhanced (P < 0.05), and transfect CAR gene can improve the cytotoxicity of MMC (P < 0.05), but not 629 (P > 0.05). Furthermore, CYP2B6 is one master enzyme for the metabolism of MMC and not 629. Transfection of CAR can increase expression of CYP2B6 mRNA in HepG2 cells, and can affect cytotoxicities of MMC and 629.
Antibiotics, Antineoplastic ; pharmacology ; Aryl Hydrocarbon Hydroxylases ; biosynthesis ; genetics ; Aziridines ; pharmacology ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Death ; drug effects ; Cell Hypoxia ; Cell Line, Tumor ; Cytochrome P-450 CYP2B6 ; Humans ; Indoles ; pharmacology ; Inhibitory Concentration 50 ; Liver Neoplasms ; metabolism ; pathology ; Mitomycin ; pharmacology ; Oxidoreductases, N-Demethylating ; biosynthesis ; genetics ; Plasmids ; RNA, Messenger ; metabolism ; Receptors, Cytoplasmic and Nuclear ; biosynthesis ; genetics ; Recombinant Proteins ; biosynthesis ; genetics ; Transcription Factors ; biosynthesis ; genetics ; Transfection

A series of 135 cases of pterygium observed at the Eye Dept. in the National Medical Center from April 1963 to May 1966, were treated with thio-tepa after the surgical removal and were studied clinically in regard to the incidence of the recurrence. Among the total series, only one case showed no response to the thio-tepa instillation and the recurrence persisted. There was a case of allergic response to the thio-tepa, which has not been found in any reports known. No serious local or systemic toxcity or any sequelae such as corneal damages, defective vision or the interference with wound healing could be observed.
Incidence ; Korea* ; Pterygium ; Recurrence ; Thiotepa ; Wound Healing

Condyloma acuminatum is a common lesion of the penis and genitalia. It uncommonly involves the urethra but when it does the lesions are difficult to eradicate. Treatment has included excision, fiuguration, podophyline and thiotepa0 none of which has been entirely successful. We report a case of intraurethral condyloma acuminatum treated with thiotepa instillation in 27 years old male patient
Adult ; Genitalia ; Humans ; Male ; Penis ; Thiotepa* ; Urethra

Clinical observation was male on 20 cases of bladder tumors treated by thio-TEPA instillations fo1lowing TUR during the period from January, 1978 through September, 1979 and the following results were obtained. Among 20 cases of bladder tumor. 1) 7cases have been followed up without recurrence. 2) 4 cages have been followed up without recurrence with instillations, who had previous recurrences following T.U.R. only. 3) 4 cases recurred in spite of 4 thio-TEPA instillations. 4) 5 cases were not followed up sufficiently.
Humans ; Male ; Recurrence ; Thiotepa* ; Urinary Bladder Neoplasms* ; Urinary Bladder*

Study group consists of 30 cases whose follow-up period is over 6 months among 32 cases of bladder tumors treated with thio-TEPA instillation following TUR during the period from January, 1978 through June, 1981. Control group consists of 25 cases whose follow-up period is over 6 months among 33 cases of bladder tumors treated by TUR only during the period from January, 1971 through December, 1977. Following results were obtained: 1. Recurrence rate: In study group, 30% In control group, 64% 2. Interval between TUR & the first recurrence: In study group, average 8.1 months In control group, average 7.1 months 3. Number of tumors at first recurrence: In study group: 89%: under 2 11%: over 3 In control group: 25%: under 2 75%: over 3
Follow-Up Studies ; Recurrence ; Thiotepa* ; Urinary Bladder Neoplasms* ; Urinary Bladder*

The results of cryotherapy for 12 cases with the tendency of recurrent pterygium treated with Thio-tepa or strontium 90 after the surgical removal are presented. There appeared the rupture of vessels. and edema following cryocautery for: 3~15 days. No special complication or any sequelae in the eyeball is observed. The irritatini signs such as foreign body sensation, lacrimation or photophobia are easily relieved with systemic treatment of Celestamin tablet.
Cryotherapy ; Edema ; Foreign Bodies ; Photophobia ; Pterygium* ; Rupture ; Sensation ; Strontium ; Thiotepa

Intravesical thio-tepa instillations for 25 patients with superficial bladder tumors were evaluated postoperatively to reconfirm its usefulness as a prophylactic agent. The over-all recurrence rate to prophylactic thio-tepa was 28%, with minor toxicity observed in 32% of the Cases. Thio-tepa Can be given safely in the postoperative period and is effective in decreasing the recurrence rate and prolonging interval free of disease of superficial bladder tumors.
Humans ; Postoperative Period ; Recurrence ; Thiotepa* ; Urinary Bladder Neoplasms* ; Urinary Bladder*