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Povzetek: The aim of the study was to investigate how the expression of tumor markers p21, p27, p53, cyclin D1, EGFR, Ki-67, and CD31 influenced the outcome of advanced inoperable oropharyngeal carcinoma patients, treated with concomitant radiochemotherapy. Patients and methods. The pretreatment biopsy specimens of 74 consecutive patients with inoperable stage IV oropharyngeal squamous cell carcinoma treated with concomitant radiochemotherapy were in retrospective study processed by immunochemistry for p21, p27, p53, cyclin D1, EGFR, Ki-67, and CD31. Disease-free survival (DFS) was assessed according to the expression of tumor markers. Results. Patients with a high expression of p21 (%10%), p27 (>50%), Ki-67 (>50%), CD31 (>130 vessels/mm2) and low expression of p53 (<10%), cyclin D1 (<10%) and EGFR (<10%) (favorable levels - FL) had better DFS than patients with a low expression of p21 (<10%), p27 (%50%), Ki-67 (%50%), CD31 (<130 vessels/mm2) and high expression of p53 (%10%), cyclin D1 (%10%) and EGFR (%10%) (unfavorable levels - UL). However, statistical significance in survival between FL and UL was achieved only for p27 and cyclin D1. DFS significantly decreased with an increasing number of markers with an unfavorable level per tumor (1%4 vs. 5%7) (78% vs. 32%, respectively; p = 0.004). The number of markers per tumor with UL of expression retained prognostic significance also in multivariate analysis. Conclusions. Statistical significance in survival between FL and UL emerged only for p27 and cyclin D1. The number of markers per tumor with UL of expression was an independent prognostic factor for an adverse outcome .
Ključne besede: oropharynx, radiochemotherapy, tumor markers
Objavljeno v DiRROS: 22.04.2024; Ogledov: 14; Prenosov: 2
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Ključne besede: electrochemotherapy, cutaneous tumors, effectiveness, tumor size, meta-analysis
Objavljeno v DiRROS: 22.03.2024; Ogledov: 95; Prenosov: 30
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Povzetek: Background. Numerous experiments have to be performed before a biomedical application is put to practical use in clinical environment. As a complementary work to in vitro, in vivo and medical experiments, we can use analytical and numerical models to represent, as realistically as possible, real biological phenomena of, in our case, electroporation. In this way we canevaluate different electrical parameters in advance, such as pulse amplitude, duration, number of pulses, or different electrode geometries. Suchnumerical models can contribute significantly to the understanding of an experiment and treatment planning as well as to the design of new electroporation devices and electrodes. Methods. We used commercially available modeling software, based on finite element method. We constructed a model of a subcutaneous tumor during electrochemotherapy (EMAS) and a model ofskin during gene electrotransfer (COMSOL Multiphysics). Tissue-electrode geometries, pulse parameters and currentvoltage measurements from in vivo experiments were used to develop and validate the models. Results. To describeadequately our in vivo observations, a tissue conductivity increase during electroporation was included in our numerical models. The output currents of the models were compared to the currents and the voltages measuredduring in vivo experiments and a good agreement was obtained. Also, when comparing the voltages needed for a successful electropermeabilization assuggested by the models, to voltages applied in experiments and achieving a successful electrochemotherapy or in vivo gene electrotransfer, good agreementcan be observed. Conclusions. Modeling of electric current and electric field distribution during cell and tissue electroporation proves to be helpful in describing different aspects of the process and allowing us to design electrodes and electroporation protocols as a part of treatment planning.
Ključne besede: electroporation, gene electrotransfer, electrochemotherapy, subcutaneous tumor, finite-element method
Objavljeno v DiRROS: 07.03.2024; Ogledov: 108; Prenosov: 31
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Povzetek: Background. Human breast cellular model, comprising four cell lines originating from spontaneously immortalized human breast epithelial MCF10A cell line, its c-Ha-ras transfectant, MCF10AT, and two tumourigenic derivatives, cultured from two sequential mouse xenographs, MCF10AT-Ca1a and MCF10AT-Ca1d, were used to compare the relative protein concentration of cathepsins and stefins in single cells. Methods. The relative protein concentration of cathepsins and stefins in single cells was analysed by confocal microscopy, and compared to their protein expression in cell homogenates. Results. The most invasive, MCF10AT cell line contained several fold higher protein concentration of cathepsin B and increased levels of stefins, but similar levels of cathepsin L, compared with the parental MCF10A cells. This was associated with five fold higher endocytosis of Matrigel-DQ-collagen IV (DQC) and a simultaneous increase in signal overlap between DQC and cathepsin L as well as DQC and stefin B, but a decrease in that of DQC and cathepsin B overlap in the MCF10AT cells. Simultaneously, increased signal overlaps between both cathepsins and between cathepsins-stefins pairs, were observed in this cell line. Conclusions. These results suggest that the increased collagen endocytosis and degradation in theinvasive phenotype significantly affect also the subcellular localization of cysteine cathepsins and stefins. Based on these and the reports of other authors, we hypothesize that the intracellular degradation may also be assoeiated with cathepsin L, whereas cathepsin B in the ras transformed breastcells is involved in both, the intracellular and pericellular degradation of extracellular matrix during cell migration and invasion.
Ključne besede: breast neoplasms, tumor cells cultured, neoplasms invasiveness, cathepsins, extracellular matrix
Objavljeno v DiRROS: 15.02.2024; Ogledov: 123; Prenosov: 35
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Ključne besede: rak (medicina), tumor, zdravljenje, citostatiki, tumorski nekrozni faktor
Objavljeno v DiRROS: 15.01.2024; Ogledov: 179; Prenosov: 48
Celotno besedilo (1,03 MB)