Cancer biochemistry biophysics最新文献

Studies have shown that meta-tetrahydroxy-phenylchlorin is an efficient tumor targeting agent for laser photodynamic therapy. The effectiveness of this approach for cancer treatment depends on drug concentration, incubation time and extracellular protein. We studied uptake and retention kinetics of mTHPC in a human fibroblast cell line. Our results clearly demonstrate a difference in the amount of extracellular mTHPC at an incubation temperature of 37 degrees C compared to 20 degrees C and 4 degrees C. pH-values were always constant and not responsible for the increase. Furthermore, both absorption and fluorescence of mTHPC increase when incubated at normal human body temperature. Incubation of human fibroblast cells with mTHPC (10 micg/mL) showed that intracellular mTHPC increases in a linear manner reaching saturation after 24 hours and declining until 48 hours with concommitant increase of supernatant mTHPC. Therefore, we believe that tumor cells can be treated optimally with PDT following a delay > 24 hours after drug administration with a minimum of damage to surrounding normal tissues.

Over 50 years ago Kögl and Erxleben reported that tumor proteins contain appreciable amounts of D-amino acids. This postulate remained highly controversial for several years, during which time several researchers either supported or refuted the hypothesis. We have analyzed several sets of tumors and normal control tissues for the presence of D-aspartate (D-Asp) and D-glutamate (D-Glu). Most tumors contain less D-Asp than the control tissues, whereas nearly half of the tumors contain 1.6 to 5.4 times more D-Glu than the controls. The tumors averaged 0.72% D-Asp and 0.61% D-Glu compared to 0.94% D-Asp and 0.35% D-Glu in the control tissues. However, within the limits of experimental error, there is no significant difference in the level of these D-amino acids between the tumors and normal tissues.

Urinary glycosaminoglycan/creatinine ratio (GAG/Cr) was determined in 42 patients with superficial bladder tumors (before and after the treatment) and in 34 healthy subjects. Before the treatment, the mean GAG/Cr ratio in patients group was not significantly different from the control group's figure (11.65 +/- 3.25 and 10.11 +/- 2.67). However, comparison of urinary GAG levels of T1 and Grade III tumors with the control group revealed statistically significant results (p<0.01 and p<0.001, respectively). All patients were previously operated by transurethral resection (TUR) and then intravesical chemotherapy applied [(BCG (n:20), 4-epidoxorubicin (n:12), interferon alpha-2 (n:10)]. Three months after the treatment, urinary GAG levels were determined. In 19 of the 24 patients whose pretreatment urinary GAG levels were higher than the control group, tumor completely remitted and their urinary GAG excretion decreased. The tumors of three cases gradually progressed and their GAG excretions were normal. Two cases hadn't any tumor mass and their urinary GAG excretion was higher than the pretreatment levels. The remaining 18 patients didn't show any clinical modification and their urinary GAG excretion did not differ from the control's and pretreatment levels. The results indicated that this test can be used as a noninvasive adjunct procedure in the follow up of patients with bladder tumors, and that urinary GAG level can not be considered as an ideal marker for bladder tumor.

The anti-cancer efficacy of dietary beta-carotene (BC, 120 mg/kg diet, daily) was evaluated during diethylnitrosamine (DEN, 200 mg/kg body weight)-induced hepatocarcinogenesis in male Sprague-Dawley rats. BC treatment was carried out throughout the study, before initiation or selection/promotion phase of hepatocarcinogenesis in a defined experimental protocol. In red blood cells (RBC) and microsomal fractions from hepatic nodular and non-nodular surrounding parenchyma, the enzymatic lipid peroxidation increased significantly by more than 3-fold, 9- to 10-fold and 4- to 7-fold respectively 18 weeks following initiation by DEN as compared to normal control animals. RBC membrane protein damage was estimated by alanine release and was found to increase more than 5-fold in the same time period in DEN control rats. A decrease in hepatic cytosolic and microsomal glucose-6-phosphatase activities was observed, whereas the activities of the oxygen-derived free-radical scavenger enzymes, like cytosolic catalase and superoxide dismutase, were shown to increase significantly at the same time point. However, BC exposure in the different phases to hepatocarcinogenesis substantially changed all the above parameters in limiting the action of DEN. Results showed that the most significant beneficial effect of BC during hepatocarcinogenesis was exerted mainly in long term continuous and/or the initiation phase of carcinogenicity, rather than in the selection/promotion phase. Moreover, the volumetric and numerical densities of the preneoplastic lesions were all appreciably reduced by exposure to BC. We conclude that long term intake of BC could reduce cancer risk by preventing hepatic lipid peroxidation and RBC membrane protein damage due to its antioxidant actions.

In this study, tissue fibronectin levels have been assayed in human prostatic cancer, benign prostatic hyperplasia and normal prostatic tissue. The mean tissue fibronectin levels for prostatic cancer, benign prostatic hyperplasia and normal groups were found to be 20.22 +/- 8.66 micrograms/mg protein and 11.77 +/- 6.74 micrograms/mg protein, respectively. In the malignant group, the mean fibronectin concentrations, appeared to be significantly higher than normal, (p < 0.05). On the other hand, fibronectin levels of benign prostatic hyperplasia were found to be statistically insignificant in comparison to the normal group (p > 0.05).

Plasma lipids and lipoprotein profiles were monitored in 72 postmenopausal and 29 premenopausal breast cancer women who were treated with tamoxifen (20 mg twice a day) for 6 months. The levels of total and free cholesterol and LDL cholesterol were markedly (P < 0.001 for each) decreased in 3 and 6 month tamoxifen-treated postmenopausal women than the baseline values of untreated breast cancer patients. On the contrary, plasma ester cholesterol, triglycerides, VLDL and HDL cholesterol levels were increased significantly in these patients. In the case of premenopausal women the lipid lowering potential of tamoxifen was markedly retarded. These results indicated that tamoxifen - treatment was more beneficial and estrogenic in postmenopausal women's lipids. In premenopausal breast cancer women, tamoxifen was antiestrogenic and less beneficial. Hence, the difference in plasma lipids and lipoprotein content was no greater among those receiving tamoxifen and baseline values of premeno - pausal women. These results indicate that tamoxifen-treatment has a more beneficial effect in postmenopausal women, with a likely reduction in cardiovascular disease, than in premenopausal subjects.

There are numerous evidences (mainly indirect) for the presence of tumor-associated surface antigens (TASA) in cells transformed by avian oncornaviruses. Hayami, et al. (1977) and Ignjatovic et al. (1978) established that such antigens on avian leukosis virus (ALV) cells have neither virus, nor oncofetal origin. On leukosis virus strain Mc31-transformed turkey cells, Filchev and Ivanov (1986) and Wesselinova (1989, 1991) also describe a TASA. But there are only a few studies on the nature and properties of such antigens (with proven antigenic properties). A TASA, induced by avian tumor viruses with MW of about 42,000 Daltons have been established on hamster cells (Aupoix et al., 1974), but there has been no further examination of it. Bauer et al. (1979) only showed that a TSSA (tumor specific surface antigen) on avian virus-transformed cells is a glycoprotein. The protein fraction we isolated from Mc31-transformed turkey tumor cells (Wesselinova, 1994) is the first attempt to characterize such purified TASA on chicken cells. After we demonstrated that it is a protein with low MW (about 14,000 Daltons) possessing antigenic properties and that it is the specific for the tumor cells, we decided to investigate its amino acid content.

In vivo antitumor activity of pirarubicin (THP) and epirubucin (EPI) in combination with doxifluridine (5'-DFUR) and cisplatin (CDDP) were examined using mouse P388 leukemia. THP (1.25-7.5 mg/kg) or EPI (1.25-15 mg/kg) was given intravenously on day 1, and then 5'-DFUR (125 or 250 mg/kg/day) and CDDP (4 mg/kg) were given orally on days 1-4 and intravenously on day 5 after tumor inoculation, respectively. Both THP and EPI enhanced the antitumor of a combination of 5'-DFUR and CDDP. The enhancement by THP was additive or synergistic, while that by EPI was additive. Cured animals were observed in the combination of THP with the two drugs, but not in that of EPI. Thus, in combination with 5'-DFUR and CDDP, THP was more effective against P388 leukemia than was EPI. The combination therapy using THP, 5'-DFUR and CDDP may be a novel chemotherapeutic approach to a variable type of tumors in clinical trials.

Recent investigation from our laboratory revealed that the estrogen receptor (ER) from breast cancer is characterized by a high molecular weight polymorphism: SDS-polyacrylamide gel electrophoresis of [3H]-tamoxifen aziridine ([3H]-TAZ) labeled cytosols usually display several bands corresponding to the native receptor (67 KDa) and lower molecular cleavage products. High frequency of such altered receptors was confirmed here by size exclusion FPLC of [125I]-E2 labeled cytosols from a series of 98 breast cancers: on the average, 60% of the ER molecules were strongly degraded (Mr < or = 37 KDa). The absence of transcriptional activating domains (ABC domains) in such receptors was further demonstrated by assessing their ability to bind to hydroxylapatite (HAP). Thus, in presence of 500 mM KCI, 55% of ERs from another series of 54 cytosols failed to strongly adsorb to this phosphocalcic matrix, a characteristic property of receptors without exposed ABC domains. Finally, [3H]-TAZ labeled cytosols from normal uterine tissue and MCF-7 human breast cancer cells growing in nude mice displayed identical multibands electrophoretic patterns revealing in both cases native and cleaved receptors. Since latter receptor forms were never detected in MCF-7 cells growing in monolayer culture, we put forward the hypothesis that they were produced under the action of proteolytic enzymes acting at the time of tissue processing. Hence, most of the truncated receptors detected in human breast cancer cytosols should not be markers of malignancy.

Rhodanese (thiosulfate: cyanide sulfurtransferase) shows distinctive mitochondrial and cytoplasmic activities in several models of tumorigenesis. To investigate the basis for these differences, the enzyme was purified from the mitochondrial and cytosolic liver fractions of mice treated with the carcinogen p-dimethyl-aminoazobenzene (DAB) and some properties were studied. Mitochondrial and cytoplasmic rhodanese exhibited different responses to the effect of ionic strength, denaturants, sulphydryl reagents, lipids and detergents, but no significant difference between enzymes purified from controls or DAB treated animals was observed. It is important to note that although chemical studies did not show very striking differences between either of the rhodanese forms, fluorescence spectral studies suggested that in DAB-treated mice, the cytosolic rhodanese would be present almost completely as the sulfur-free form, while the mitochondrial enzyme would be present as the sulfur-substituted form. These findings would justify the high rhodanese activity present in mitochondria. On the other hand, in control animals, rhodanese would exist only as the partial sulfur-substituted form in both fractions.