The effect of combined therapy on activity of cathepsin D and alpha-1-antitrypsin in the blood serum of women with cervical cancer

Purpose of investigation: The aim of the study was to determine the activity of cathepsin D (CTSD) and alpha-1-antitrypsin (AAT) in the blood serum of women with cervical carcinoma treated with different modes of therapy. Methods: The study was conducted on 68 women suffering from carcinoma of the uterine cervix, that were irradiated intracavitarily by a Selectron LDR brachytherapy unit. Additionally, all patients were treated with different therapy methods according to clinical stage. Results: In women with cervical cancer, CTSD activity was higher while AAT activity was lower both before and after brachytherapy sessions as compared to controls. Six months after the end of therapy, the activity of CTSD and AAT reverted back to the values characteristic for healthy women. Conclusion: The estimation of cathepsin D and alpha-1-antitrypsin activity during the course of cervical cancer management may be useful in early detection of potential recurrence and/or widespread metastasis formation.

Cathepsin D; Alpha-1-antitrypsin; Cervical cancer; Therapy

[1] Landoni F., Maneo A., Colombo A., Placa F., Milani R., Perego P. et al.: “Randomised study of radical surgery versus radiotherapy for Stage Ib-IIa cervical cancer”. Lancet, 1997, 23, 535.

[2] Urban´ski K., Gasin´ska A., Pudelek J., Fowler J.F., Lind B., Brahme A.: “Biologically effective doses in radiotherapy of cervical carcinoma”. Neoplasma, 2004, 51, 228.

[3] Szyman´ski W., Makasewicz-Guzikowska J., Grabiec M.: “Results of cervix cancer treatment by means of prooperative cesium therapy”. Med. Sci. Monit., 1996, 2, 61.

[4] Bidzin´ski M.: „Diagnostyka nowotworów szyjki i trzonu macicy oraz jajników”. Nowotwory, 1995, 45, 33.

[5] Scambia G., Benedetti P. , Foti E., Ferrandina G., Leone F.P., Marciano M., Mancuso S.: “Multiple tumour marker assays in advanced cervical cancer: relationship to chemotherapy response and clinical outcome”. Eur. J. Cancer, 1996, 32, 259.

[6] Makarewicz R., Drewa G.: “A possible application of cathepsin B activity determination for estimating the spread of the cervix uteri carcinoma”. Acta Biochim. Pol., 1996, 43, 521.

[7] Anson M.L.: “The estimation of pepsin, trypsin, papain and cathepsin with hemoglobin”. J. Gen. Physiol., 1939, 22, 79.

[8] Eriksson S.: “Studies in alpha 1-antitrypsin deficiency”. Acta Med. Scand., 1965, 432, 1.

[9] Tsukuba T., Okamoto K., Yasuda Y., Morikawa W., Nakanishi H., Yamamoto K.: “New functional aspects of cathepsin D and cathepsin E”. Mol. Cells, 2000, 10, 601.

[10] Heylen N., Vincent L.M., Devos V., Dubois V., Remacle C., Trouet A.: “Fibroblasts capture cathepsin D secreted by breast cancer cells: possible role in the regulation of the invasive process”. Int. J. Oncol., 2002, 20, 761.

[11] Vitaioli L., Baldoni E., Ricci R. Indraccolo SR.: “Expression of acidic glycosphingolipids and arylsulphatase A activity in human pathological endometrium”. Eur. J. Obstet. Gynecol. Reprod. Biol., 1994, 54, 31.

[12] Alekseev G.I., Korovkin B.F., Mikhaleva N.P., Fedotov G.M.: “Effect of lethal and superlethal doses of gamma-irradiation on the lysosomal enzymes activity in radio-sensitive and radio-resistant tissue in the rat”. Vopr. Med. Khim., 1984, 30, 95.

[13] Woz´niak A., Drewa T., Rozwodowska M., Drewa G., Lambrecht W., Wis´niewska I.: “Activity of some lysosomal neyzmes in serum and in tumors of patients with squamous cell lung carcinoma”. Neoplasma, 2002, 49, 6.

[14] Bhuvarahamurthy V., Govindasamy S.: “Extracellular matrix components and proteolytic enzymes in uterine cervical carcinoma”. Mol. Cell. Biochem., 1995, 144, 35.

[15] Makarewicz R., Drewa G., Szymanski W., Skonieczna- Makarewicz I.: “Cathepsin B in predicting the extent of the cervix carcinoma”. Neoplasma, 1995, 42, 21.

[16] Markovic O., Markovic N.: “Cervical acid phosphatase: a biomarker of cervical dysplasia and a potential surrogate endpoint for colposcopy”. Dis. Markers, 2003, 19, 279.

[17] Utrera-Barillas D., Salcedo-Vargas M., Gariglio-Vidal P., Hernández-Hernández D.M., Gutiérrez-Delgado F., Benítez-Bribiesca L.: “H-ras and Nm23-H1 gene expression and proteolytic activity in squamous cell carcinoma of the uterine cervix”. Arch. Med. Res., 2000, 31, 172.

[18] Bhattacharyya J., Chaudhuri L.: “Alpha 1-antitrypsin: a possible tool for diagnosis of cervical cancer”. Biochem. Med. Metab. Biol., 1990, 43, 243.

[19] Möschl P., Lubec G.: “Basement membrane degradation by enzymes of the 8000-g-lysosome fraction from cervical cancer cells”. Onkologie, 1981, 4, 137.