[Trastuzumab in the breast cancer treatment: efficacy and resistance mechanisms].

Trastuzumab, a humanized monoclonal antibody against the HER-2 receptor, was the first targeted therapy for HER-2 positive breast cancer. The treatment of HER-2 positive breast cancer in monotherapy, but mainly in combination with cytostatics trastuzumab, showed significant efficacy and increased the time to progression/relapse and overall survival. On the other hand, despite it being administered to only a selected patient population, the response rate varies in range and duration due to the primary or acquired tumor resistance to trastuzumab.

Prediction of ovarian cancer prognosis and response to chemotherapy by a serum-based multiparametric biomarker panel.

Currently, there are no effective biomarkers for ovarian cancer prognosis or prediction of therapeutic response. The objective of this study was to examine a panel of 10 serum biochemical parameters for their ability to predict response to chemotherapy, progression and survival of ovarian cancer patients. Sera from ovarian cancer patients were collected prior and during chemotherapy and were analysed by enzyme-linked immunosorbent assay for CA125, kallikreins 5, 6, 7, 8, 10 and 11, B7-H4, regenerating protein IV and Spondin-2.

[A retrospective analysis of trastuzumab-based therapy in metastatic breast cancer patients at Masaryk Memorial Cancer Institute. Identification of predictive factors].

Introduction: Trastuzumab is a humanized monoclonal antibody directed against the HER-2 receptor. Trastuzumab-based therapy significantly improves response rate (RR), time to progression (TTP) and overall survival (OS) for women with HER-2 positive metastatic breast cancer. Despite its initial efficacy, acquired resistance to trastuzumab develops in a majority of patients with MBC, and a large subset never responds, demonstrating primary resistance.

[Symptomatic Meckel's diverticulum in children].

Meckel's diverticulum (MD) is the most frequent anomaly of the small intestine, usually asymptotic. Complications of MD in children are usually bleeding and inflammation. Signs are non specific and diagnostics is prolonged.

Malignant melanoma associates with Th1/Th2 imbalance that coincides with disease progression and immunotherapy response.

The immunological dysfunction associated with human cancer is well known phenomenon. It comprises number of pathological changes within immune network including imbalance in cytokines of Th1/Th2 origin. The objectives of our study were (i) to evaluate the abnormalities in serum levels of selected cytokines in malignant melanoma patients with regional lymph node metastases as compared to normal values, (ii) to examine the relationship between postoperative cytokine levels and disease progression and (iii) to correlate cytokine profile changes during IFN-alpha therapy with the disease progression and potential therapeutical response.

Tiptoeing to chromosome tips: facts, promises and perils of today's human telomere biology.

The past decade has witnessed an explosion of knowledge concerning the structure and function of chromosome terminal structures-telomeres. Today's telomere research has advanced from a pure descriptive approach of DNA and protein components to an elementary understanding of telomere metabolism, and now to promising applications in medicine. These applications include 'passive' ones, among which the use of analysis of telomeres and telomerase (a cellular reverse transcriptase that synthesizes telomeres) for cancer diagnostics is the best known.

Release of cytokeratin-18 and -19 fragments (TPS and CYFRA 21-1) into the extracellular space during apoptosis.

Serum fragments of cytokeratins-18 and -19 (measured as TPS and CYFRA 21-1, respectively) have traditionally been considered as markers of tumor proliferation, although the evidence is scarce for a causative relationship between proliferation and levels of TPS and CYFRA 21-1. We examined whether apoptosis might produce TPS and CYFRA 21-1 fragments. MCF-7 breast cancer cells were treated with mitomycin C or agonistic anti-CD95 antibody, and levels of TPS and CYFRA 21-1 in tissue culture supernatants were compared with the frequency of cells exhibiting the following markers of cell death: intracellular cytokeratin-18 cleavage, surface staining with annexin-V, propidium iodide uptake, DNA fragmentation.

Quantitative determination of telomerase activity in breast cancer and benign breast diseases.

Telomerase plays an important role in maintaining the stability of chromosomes. This ribonucleoprotein prevents chromosome ends (telomeres) from gradual loss with each cell division. It enables tumor cells to maintain telomere length, allowing indefinite replicative capacity.

Homocysteine in breast cyst fluid.

Background: Elevated plasma homocysteine concentrations have been reported in a variety of carcinoma, including those of the breast. The risk of breast cancer is higher in patients suffering from gross cystic disease. The breast cyst fluid contains unusual amounts of low- and high- molecular substances, including steroid hormones and their conjugates.

Relation of prenephrectomy CD profiles and serum cytokines to the disease outcome and response to IFN-alpha/IL-2 therapy in renal cell carcinoma patients.

Immune parameters, including cytokine levels and CD profiles were determined in 78 renal cell carcinoma patients (RCC) prior to nephrectomy. The values were correlated with the outcome of disease and response to cytokine-based treatment during a 3-year follow-up. Significantly lower frequency of progressions and higher proportion of survivors were recorded in 24 treated patients compared to 43 untreated ones (22.

Renal cell carcinoma-associated immune impairment that may interfere with the response to cytokine therapy.

This prospective study was carried out to explore cytokine-related immune alterations in 69 renal cell carcinoma patients (RCC) and to look for changes which might potentially serve as a reliable predictors of response to cytokine-based therapy. Interleukin-2 (IL-2), its soluble receptor (sIL-2R) and tumor necrosis factor (TNF-alpha) levels produced in vitro by PHA activated and intact mononuclear cells (PBMC) were determined. Concentrations of IL-2, IL-4, IL-6, sIL-2R, TNF-alpha and CRP were measured in sera.

Significance of pre-treatment immunological parameters in colorectal cancer patients with unresectable metastases to the liver.

Background/aims: In this study, we have compared the profiles of peripheral blood lymphocyte (PBL) subsets and serum cytokine levels of healthy individuals with those of patients with unresectable liver metastases from colorectal carcinoma before starting regional chemoimmunotherapy. Since the therapeutic responses are limited only to a subset of patients, we hypothesize that the initial status of immunity and individual immune response to a tumor might be significant to the therapeutic outcome.

Methodology: Cellular and humoral immunological parameters were compared between 10 patients with colorectal cancer metastases to the liver responding and non-responding to regional intra-arterial chemo-immunotherapy, and 5 healty individuals.

Phylloid breast tumors and three steroid hormone receptors.

The concentrations of three steroid hormones (estrogen, progesteron and 1,25-dihydroxycholecalciferol) receptors (ER, PgR, DR) in tissue cytosol were analyzed in a group of 17 breast phylloid tumors. Comparison with breast carcinoma tissue samples (n = 37) did not reveal significant differences in average values of ER, PgR, and DR. Comparison with another control set of 30 samples of dysplastic tissue of the mammary gland showed significant differences only in PgR values.

Early diagnosis of breast cancer dissemination by tumor markers follow-up and method of prediction.

A mathematical model of prediction of progression was tested in patients with breast cancer employing long-term monitoring of tumor markers CEA, CA 15-3, MCA and TPA, erythrocyte sedimentation rate (FW), and the enzymes gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and lactate dehydrogenase (LD) in serum. At the same time, specificity, sensitivity, lead time and positive predictive value were evaluated along with false positivity for all these parameters and their combinations. A model was proposed for the follow-up of patients with breast cancer after the completion of basic therapy.

Polyclonal antibodies to human milk caseins.

Preparations of total human casein and its individual fractions were isolated for production of specific polyclonal antibodies. Immunization procedures used differed in the schedule for antigen administration, antigen concentrations, degree of additional purification, and modification of the size of molecules. Immunoprecipitation techniques failed to provide an unambiguous proof of the presence of antibodies to human milk caseins in antisera even after immunization of animals phylogenetically considerably different from man.

Carcinoembryonic antigen and alpha-lactalbumin in phylloid tumor tissues.

The concentration of carcinoembryonic antigen and alpha-lactalbumin in tumor tissue cytosol were analyzed in a group of 19 tumors of cystosarcoma phyllodes type. Both antigens were also localized in the tissue of identical tumors by means of immunohistochemical procedure. The cytosol levels of both proteins were found to be higher in the histologically defined malignant type of phylloid tumors.

Complex biochemical analysis of human breast tumor tissue.

The quantitative biochemical analysis of tissue specimens from 76 human breast carcinomas consisted of examination for cytosolic estrogen receptors (cER), nuclear estrogen receptors (nER), progesterone receptors (PgR), 1,25-dihydroxycholecalciferol receptors (DR), carcinoembryonic antigen (CEA), alpha-lactalbumin (aLA), and gamma-glutamyl transferase (gGT). The highest incidence was found in CEA (76%), DR (70%), and aLA (62%). There was a high percentage of tumors containing only DR, in contrast to the tumors containing only cER or PgR.

Immunohistochemical localization of alpha-lactalbumin in human breast cancer tissue.

One hundred and eleven formalin-fixed breast cancer tissue samples were examined for the presence of alpha-lactalbumin using our polyclonal antibodies to this specific milk protein. Alpha-lactalbumin was shown to be present in 67 tumor samples (60%), in 15% of cases the occurrence of alpha-lactalbumin was questionable. No relationship was found between alpha-lactalbumin positivity and the histological type of the tumor, differentiation grading, type of invasivity, or stromal reactivity.

A non-competitive enzyme immunoassay of human alpha-lactalbumin in biological fluids and tissue extracts.

A sandwich non-competitive enzyme immunoassay for the measurement of human alpha-lactalbumin in serum, milk, and tumour tissue cytosol was developed using affinity-purified polyclonal antibody adsorbed to solid phase. The detection limits of this procedure in tubes (macromethod) and in wells of microtitre plates (micromethod) are 50 pg and 25 pg/sample, respectively, which means 2.5 micrograms/l of serum at appropriate dilution.

Biosynthesis of nuclear RNAs during 3'-methyl-4-dimethyl-aminoazobenzene hepatocarcinogenesis and in transplantable rat hepatomas.

The long-term administration of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) to rats causes marked changes in concentrations and synthesis of nucleic acids in the liver. In the beginning, a decrease in total cellular RNA concentration can be seen. On the other hand, at the stage of tumor onset the concentration of nuclear RNAs in precancerous lesions and hepatomas is elevated.

Induction of chromosome shattering and micronuclei by ultraviolet light and caffeine. I. Temporal relationship and antagonistic effects of the four deoxyribonucleosides.

It is known that nucleosides may have antimutagenic and anticlastogenic effects. Here, we have investigated the influence of nucleosides on the induction of shattered chromosomes (fragmentation and/or pulverization of chromosomes of a mitotic cell) and of micronuclei by ultraviolet (UV) light and caffeine. Asynchronous cell cultures of a V79 subline of the Chinese hamster were irradiated at wavelength 254 nm using fluences up to 5.

Correlation of deoxycytidylate deaminase activity with cell proliferation during hepatocarcinogenesis and tumour growth in transplantable rat hepatomas.

Determination of activity of deoxycytidylate deaminase stabilized by etylene glycol was used to evaluate the rate of DNA synthesis in precancerous liver tissue and in transplantable rat hepatomas. Increased activity of the enzyme in macroscopically unchanged liver tissue occurred during hepatocarcinogenesis induced by 3'-Me-DAB in the period between weeks 1 and 10. The slow growing transplantable tumours derived from primary hepatomas induced by DAB and AF showed slightly increased activity, while the fast growing lines derived from primary tumours induced by 3'-Me-DAB were characterized by markedly increased activity.