Cancer biochemistry biophysics最新文献

Mucin is a viscous secretion of glycoproteins secreted by epithelial cells of normal and cancerous tissues. Excessive and abnormal mucin synthesis has been observed in a number of cancers. The conformation and configuration of the surface carbohydrates play a key role in generating multiple forms of mucins in different cancers. The epitopes on the surface of mucin are recognized by antibodies present in different cancer cells. The primary structure of some of the cancer-associated mucins has been determined by molecular cloning of their complementary DNAs. The detection methods for cancer-associated mucins and their clinical applications are discussed.

The activity of the protein tyrosine kinase pp60c-src was determined for each of the 60 human cell lines in the panel used by the National Cancer Institute for the random screening of potential anticancer drugs. The leukemia, lymphoma, melanoma, and small-cell lung cancer derived cell lines had low pp60c-src activity. Surprisingly, non-small-cell lung and ovarian cell lines had a median pp60c-src activity which was greater than that of the panel of cells representing colon cancer, which is most often associated with elevated pp60c-src activity. This data defines homologous cell lines which contain low and high pp60c-src activity which will aid attempts to understand the role of this enzyme in human cancer.

Most of breast cancer patients are treated with CMF, which is a combination of three anticancer agents, cyclophosphamide, methotrexate and 5-fluorouracil. Metabolites of CMF induce lipid peroxidation by inactivating the antioxidant enzymes, thereby rendering the system inefficient in management of the free radical attack. Acrolein and phosphoramide mustard are the metabolites of cyclophosphamide which are among the causative agents which reduce the activity of superoxide dismultase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase in erythrocytes of CMF treated breast cancer patients.

Recently, lipoprotein (a) [Lp (a)] levels were found to be elevated in various types of cancer. This study was designed to evaluate the role of serum Lp (a) in early and advanced stages of breast cancer. Fasting venous blood samples were collected from 18 patients with Stage I, and 21 patients with Stage IV disease and were analysed for Lp (a). The results were compared with data from 22 healthy female controls. Patients with both Stage 1 and Stage IV disease had significantly higher (p < 0.001) Lp (a) concentrations than did healthy controls. Lp (a) was also found to be significantly elevated in Stage IV patients when compared with the Stage I group. Our data suggest that there is a highly significant association between Lp (a) and the presence and progression of breast cancer, and the serum Lp (a) determination may provide an aid in patients with breast cancer for both diagnostic purposes and the follow-up of the disease.

We have examined the therapeutic effects of combination therapy of pirarubicin ((2"R)-4'-O-tetrahydropyranyladriamycin, THP) with various antitumor agents against P388 murine leukemia. THP showed a high antitumor activity in combination with various antitumor drugs, especially with cyclophosphamide (CPM), cisplatin (CDDP), mitomycin C (MMC), enocitabine (BHAC), vindesine (VDS) or methotrexate (MTX). The effects of combination therapy depended on the order of administration of THP and combined drugs. THP-preceding treatment gave more synergistic effects in combination with 5-fluorouracil (5-FU) or MTX. THP-preceding or simultaneous treatment with etoposide (ETP) indicated the higher synergistic activity than ETP-preceding one. Moreover, THP showed much higher synergistic effects in any order of the combination with CPM, CDDP, MMC, BHAC, VDS or MTX. These results suggest that THP possesses a therapeutic usefulness clinically in combination with various antitumor drugs, if the selection of drugs combined with THP and the order of administration are suitable.

Queuosine (Q nucleoside) is a highly modified guanosine analog and is present only in the first position of the anticodons of tRNA(Tyr), tRNA(His), tRNA(Asn) and tRNA(Asp). The levels of Q in normal human brain and two different types of human brain tumors (meningiomas and astrocytomas) were determined by using an enzymatic assay method. tRNAs isolated from tumor tissues contained decrease amounts of Q when compared to tRNAs from normal (i.e. non-tumor) brain tissue. There was a relationship between the levels of Q nucleoside and the tumor malignancy in the sense that the deficiency was greater in the highly malignant astrocytomas compared to meningiomas which are usually benign tumors. Increased Q deficiency was also observed in higher grade tumors.

N-acetyl-beta-glucosaminidase (NAG) and its isoenzymes were measured in 60 patients with breast cancer and in 30 patients suffering from benign breast tumors. NAG activity was significantly increased (P < 0.001) in cancer patients. The concentration of isoenzyme A always exceeded that of isoenzyme B, but isoenzyme B concentration was significantly (p < 0.001) higher in patients than in controls. An intermediate form, I, was more evident but not significant in patients. Evaluation of the predictive value of the NAG isoenzyme B, revealed a good sensitivity, efficiency and specificity. It seems from this study that the determination of the isoenzyme NAG B activity may be useful for better diagnosis of breast cancer.

We showed that massive growth of mouse Ehrlich ascites carcinoma (EAC) cells was not inhibited by wool grease secreted from the sheep sebaceous gland, whereas wool fatty acids separated by saponification of wool grease was growth-inhibitory. We then fractionated wool fatty acids into 9 fractions using molecular distillation (80-200 degrees C; 1 x 10(-2) mmHg) and found a marked antitumor activity in a low-boiling-point (< 80 degrees C) fraction (MW 200-300; C10-C20), which was further separated by reversed phase liquid chromatography on an octadecylisilica gel column, resulting in 5 fractions. The second most hydrophobic fraction (C8Si-4) obtained was the most growth-inhibitory to EAC cells cultured or implanted into mice, more marked than the antitumor glycopeptide bleomycin. C8Si-4 was suggested to be a mixture of a normal-chain C16-saturated fatty acid and two branched-chain kinds of saturated C16-iso- and C19-anteiso-fatty acids without hydroxyl groups according to gas chromatography-mass spectrographic analysis. Thus low-boiling-point saturated fatty acid moieties in some wool grease molecules were shown to become growth-inhibitory in vitro and in vivo only after released in the free acid form by esterolysis.

The influence of divalent cations on estrogen and androgen binding in human benign prostatic hypertrophy (BPH) was investigated. Two tissue types were detected. In type I, important estradiol binding increase in the presence of Mg++ and good evidence of the androgen receptors were noticed. Type II tissues were characterized by weak or inhibitory effect of Mg++ and, poor detection of the androgen receptors in some of the buffers used. Zn++ inhibited estradiol binding. Effects of chelators leaving some endogenous divalent cations in the medium were investigated. For both binding activities no difference could be established between type I and type II tissues. One exception was a somewhat increased androgen binding for type II when endogenous Mg++ was present. Strong inhibition of estradiol binding in the presence of EDTA + Mg++ always occurred. Influence of divalent cations on steroid binding measurements in BPH tissues is discussed.