Metastatic cancer elevated liver enzymes
The biological potential of malignant tumors is an important factor in their growth. The malignant phenotype is asociated with the combined action of some exo- or endopeptidases, such as cathepsin D. They constitute an enzymatic cascade which facilitates extracellular matrix degradation, an important stage in the invasion by tumor cells. In our study we applied a biochemical method to determine cathepsin D in the tumoral cytosol prepared from the tumor sampled between the 13th and 25th day.
The enhanced enzyme activity in the tumor tissue is consistent with the cathepsin D role in metastasis appearance and development. Potenţialul biologic propriu tumorilor maligne este un factor important în evoluţia acestora. Acestea formează o cascadă enzimatică prin care se facilitează degradarea matricei extracelulare, etapă importantă în invazia tumorală. În acest studiu am determinat printr-o metodă biochimică catepsina D în citosolul tumoral, obţinut din tumora primară recoltată între a a şi a a zi.
Prezenţa în ţesutul metastatic cancer elevated liver enzymes a unei activităţi enzimatice crescute confirmă rolul catepsinei D în procesul de metastazare.
Clinical trials
The development of sofisticated biochemical, immunological and genetic techniques that can be applied to spontaneous primary tumors and their metastases was an important stage in research and led to the detailed analysis of the tumoral progression, matastasis and therapy of the cancerous disease and its metastases.
For metastatic cancer elevated liver enzymes the experimental tumor metastases, it is certainly useful to have animal tumor models that mimic well the metastatic disease in humans. Some of these medels can have a limited usefulness and answer to some specific questions regarding the metastatic process, while others can be useful in studying a large area of problems related to cancer biology and metastases therapy.
Walker carcinosarcoma is a tumor that appears spontaneously in the mammary glands of the rat, discovered by Walker. Initially, the tumor was diagnosticated as adenocarcinoma, in which structure there is also a sarcomatoid cell type population.
Walker carcinosarcoma is supported by subcutaneous grafts in Wistar rats, it has a metastatic potential, and the invasion of locoregional lymph nodes appears in the terminal phase of the tumoral growth, when tumor necrosis metastatic cancer elevated liver enzymes are accentuated.
It is a standard tumor helminth infection in lymph node metastasis models, in the preclinical screening of the antitumor substances, and also in different experimental models of chemotherapy and radiation therapy.
The goal of our study was to elucidate the activity of cathepsin D, correlated with evolution and metastasis parameters.
Materials and method Biological samples The study was conducted on 60 normal, healthy Wistar albino rats, with a g medium weight, who were inoculated with 1, Cell viability was assessed using 0.
Rats were sacrificed at 13, 15, 18, 21 and 25 days from grafts, when the primary ciuperci kombucha was evaluated and biologic tissue was sampled for obtaining the tumor cytosol.
The homogenate was centrifuged at xg, for 10 minutes, and the supernatant was ultracentrifuged at xg for one hour. Determinations The cytosolic protein concentration was determined by two methods, Lowry and Bradford, metastatic cancer elevated liver enzymes bovine serum albumin BSA as standard.
The method used for the biochemical determination of the cathepsin D was similar to the method described by Metastatic cancer elevated liver enzymes. The reaction took place in Acetate Buffer 1M pH 3. A standard curve was made, for whose plotting we used pure cathepsin D, obtained from Sigma company. For control, 20 µl of pepsatin A were added metastatic cancer elevated liver enzymes the reaction, resulting a final concentration of M.
A second control sample was realized, adding the tumor extract followed by the trichloroacetic acid, which stopped the reaction. Tabelul 1; The assessment of hepatic metastases in Wistar rats Tabelul 2; The activity of cathepsin D in Walker carcinosarcoma Results and discussion Walker carcinosarcoma had a good growth, the tumor became palpable at days after the inoculation, and the micrometastases were present in the liver.
At days after the inoculation we could notice hepatic macrometastases. The evolution and metastatic process of the Walker carcinosarcoma were assessed by measuring the tumor volume and by the quantitative evaluation of the hepatic tumors. Table 1 presents the evaluation of hepatic metastases, in the evolution course of Walker carcinosarcomain Wistar rats subcutaneously grafted with 1x living cells.
Clinical Trials Register
The results presented in Table 1 are means obtained from two lots grafted at different moments, in which the rats presented quite similar evolutions. The 15th day can be considered the moment metastatic cancer elevated liver enzymes the obvious appearance of liver metastases in our experimental conditions. From the primary tumor sampled in days 13, 15, 18, 21 and 25 it was prepared the tumor cytosol in which there were dosed the cytosolic protein and the cathepsin D. The results presented in Table 2 indicate the modification of this degradative enzyme in the primary tumor, subcutaneously grafted, in the process of enzyme formation.
A significant increase of the enzyme activity was noticed in the 15th day, compared to the activity measured at 13 days after inoculation. The differences in the cathepsin D activity, in the primary tumor, in days 15, 18, 21 and 25 are elevated, with statistical significance. Cathepsin D activity is 2. The presence in the tumoral tissue of an enhanced enzymatic activity of cathepsin D, in a metastasizing tumor such as Walker carcinosarcomais in agreement with the presumed role of cathepsin D in the metastasis process.
Conclusions It was noticed a positive correlation between the metastatic cancer elevated liver enzymes time of lysosomal enzyme, cathepsin D, in Walker carcinosarcomaand the appearance of micro- and macrometastases in liver.
Expresia catepsinei D în carcinosarcomul Walker-256 şi rolul ei în procesul de metastazare
The mechanisms responsible for the intratumoral lysosomal enzyme growth are unidentified, but they might be related to macrophage infiltration and other tumor-host interactions, which can facilitate the tumor cell disemination.
Our results suggest that the inhibition of this enzyme may open the way for new therapeutic methods for controlling the malignant disease.
Bibliografie 1. Lucian Miron. Oncologie generală, Ed. Nota Zece, Factori moleculari ai metastazării tumorale, Ed. Universităţii Bucureşti, Molecular Mechanism of Cancer, Springer, Olinici CD.
Biologia celulară a cancerului, Ed. Medicală, Bucureşti, Mona Mostafa Mohamed, Bonnie F. Cysteine cathepsins: multifunctional enzymes in cancer, Nature publishing Group, Vol. Cysteine proteases of parasitic organisms. Mol Biochem. Parasitol, McKerrow JH. Development of cysteine protease inhibitors as chemotherapy for parasitic diseases: metastatic cancer elevated liver enzymes on safety, target validation, and mechanism of action.
Parasitol,29, —7. Saftig P et al. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Sci,USA 95, —8. Shi GP et al. Immunity 10,— Roth W et al. Cathepsin L deficiency as molecular defect of furle hyperproliferation of keratinocyte sand pertubation of metastatic cancer elevated liver enzymes follicle cycling.
Stypmann J et al.
Dilated cardiomyopathy in mice deficient for the lysosomal cysteine peptidase cathepsin L. Natl Acad. Sci,USA 99, —9. Towards specific functions of lysosomal cysteine peptidases: phenotypes of mice deficient for cathepsin B or cathepsin L.
Individual cathepsins degrade immune complexes internalized by antigen-presenting cells via Fcγ receptors. Felbor U et al.
Expresia catepsinei D în carcinosarcomul Walker-256 şi rolul ei în procesul de metastazare
Neuronal loss and brain atrophy in mice lacking cathepsins B and L. Dipeptidyl peptidase I is required for metastatic cancer elevated liver enzymes processing and activation of granzymes A and B in vivo.
USA,96, — Caughey GH. New developments in the genetics and activation of mast cell proteases. Xia L et al.
Localization of rat cathepsin K in osteoclasts and resorption pits: inhibition of bone resorption and cathepsin K-activity by peptidyl vinyl sulfones. Friedrichs B et al. Thyroid functions of mouse cathepsins B, K, and L, J. Hughes SJ et al.
- Definition of glycopeptide antibiotic - NCI Drug Dictionary - National Cancer Institute
- Eur Arch Otorhinolaryngol ; 2 :Feb.
- Parazitii intestinali si balonarea
- Expresia catepsinei D în carcinosarcomul Walker şi rolul ei în procesul de metastazare
- Expresia catepsinei D în carcinosarcomul Walker şi rolul ei în procesul de metastazare
- Analize toxoplasmoza
- Warts human papilloma plantar
A novel amplicon at 8p22—23 results in overexpression of cathepsin B in metastatic cancer elevated liver enzymes adenocarcinoma. Lin Metastatic cancer elevated liver enzymes cancer elevated liver enzymes et al.
A minimal critical region of the 8p22—23 amplicon in esophageal adenocarcinomas defined using sequence tagged site-amplification mapping and quantitative polymerase chain reaction includes the GATA-4 gene. Cancer Res. Gene, —9. Gene, 83— Identification and characterization of a novel human cathepsin L splice variant. Gene, — Molecular regulation of human cathepsin B: implication in pathologies. Oncobiologie, Ed. Ars Docendi, Bucureşti,
