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493. Cysteine cathepsins, stefins and extracellular matrix degradation during invasion of transformed human breast cell linesIrena Zajc, Aleš Bervar, Tamara Lah Turnšek, 2006, original scientific article Abstract: 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.
Keywords: breast neoplasms, tumor cells cultured, neoplasms invasiveness, cathepsins, extracellular matrix
Published in DiRROS: 15.02.2024; Views: 122; Downloads: 35
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495. Preoperative concomitant chemoradiotherapy in esophageal cancerBoštjan Šeruga, Mihael Sok, Janez Eržen, Jože Jerman, Boris Jančar, Branko Zakotnik, 2006, original scientific article Abstract: Background. Currently primary treatment options for esophageal cancer are surgery only or concomitant chemoradiotherapy (CRT) and the long-term survivalof patients with locally advanced disease is rare. Preoperative concomitant CRT seems to be beneficial, mostly in patients who achieve a complete pathologic response (pCR) after CRT. In this retrospective analysis the efficiency and toxicity of preoperative CRT in patients with locally advanced esophageal cancer was analysed as well as the influence of pCR on thesuraival. Patients and metkods From 1996 to 2002 41 patients with locoregionally confined esophageal cancerwere treated with cisplatin 75 mgžm2 and 5-FU 1000 mgžm2 as 4 day contonuous infusion starting on days 1. and 22. with concorrtitant radiotherapy 4500 cGy, 200-300 cGyžday. Esophagectomy followed 4-5 weeks after radiotherapy. After the surgery patients were followed-up regularly at 3-6 months intervals. Results. The pCR was achieved in 26.8% of patients. The overall median survival time was 18 months for all patients, 21.2 months for patients who achieved pCR and 16 months in those with residual disease (p= 0,79). Postoperative mortality rate was 22%. The median dose intensity for cisplatin was 92% and for 5-FU 71.5 of the planned dose. Disease recurred most often locoregionally (31.7%) and the overall recurrence rate was 43.9. Conclusion. Modern radiation techniques and the adequate dose intensity could further improve the locoregional control. The selection of patients without comorbid conditions and without already present distant metastases is essential for this combined treatment approach.
Published in DiRROS: 15.02.2024; Views: 123; Downloads: 33
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496. Schedule-dependency of doxorubicin and vinblastine in EAT tumours in miceMarija Auersperg, Ana Pogačnik, Veronika Kloboves-Prevodnik, Gregor Serša, Maja Čemažar, 2006, original scientific article Abstract: Background. Antitumour schedule-dependency of the doxorubicin and vinblastine combination was explored. Materials and methods. Intraperitoneal Ehrlich ascites tumours (EAT) syngeneic to CBA mice were treated with vinblastine ar doxorubicin alone, or in combined treatment schedules. Results. Combinations of doxorubicin and vinblasfine administered at 48-h, but not at 24-h interval,regardless of the sequence of drugs, significantly reduced the numberof tumour cells in the ascites in corrtparison with all other treatments. In the combined treatment schedules, the predominant morphologicalchanges as well as DNA distribution pattern were dependent on thefirst drug applied. Regardless of the sequence of the drugs, median survival times of animals did not significantly differ between the treatment groups. Conclusions. The effect of combination of vinblastine and doxorubicin is schedule-dependent. The time interval, but not the sequence of drugs seems to be crucial for the observed effect. The data from preclinical studies are important for planning combined treatment schedules in clinical setting.
Published in DiRROS: 15.02.2024; Views: 103; Downloads: 23
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497. Mixed Riemann-Hilbert boundary value problem with simply connected fibersMiran Černe, 2024, original scientific article Abstract: We study the existence of solutions of mixed Riemann-Hilbert or Cherepanov boundary value problem with simply connected fibers on the unit disk $\Delta$. Let ▫$L$▫ be a closed arc on $\partial\Delta$ with the end points $\omega_{-1}, \omega_1$ and let $a$ be a smooth function on $L$ with no zeros. Let $\{\gamma_{\xi}\}_{\xi\in\partial\Delta\setminus\mathring{L}}$ be a smooth family of smooth Jordan curves in $\mathbb C$ which all contain point $0$ in their interiors and such that $\gamma_{\omega_{-1}}$, $\gamma_{\omega_{1}}$ are strongly starshaped with respect to $0$. Then under condition that for each $w\in \gamma_{\omega_{\pm 1}}$ the angle between $w$ and the normal to $\gamma_{\omega_{\pm 1}}$ at $w$ is less than $\frac{\pi}{10}$, there exists a Hölder continuous function $f$ on $\overline{\Delta}$, holomorphic on $\Delta$, such that ${\rm Re}(\overline{a(\xi)} f(\xi)) = 0$ on $L$ and $f(\xi)\in\gamma_{\xi}$ on $\partial\Delta\setminus\mathring{L}$.
Keywords: boundary value problems, mixed Riemann-Hilbert problem, Cherepanov problem
Published in DiRROS: 15.02.2024; Views: 117; Downloads: 57
Full text (467,68 KB)
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