[Changes in the CD8+ Density of Tumor Infiltrating Lymphocytes after Neoadjuvant Radiochemotherapy in Patients with Rectal Adenocarcinom]. / Vliv predoperacní radiochemoterapie na hustotu CD8+ tumor infiltrujících lymfocytu adenokarcinomu rekta.

BACKGROUND: The goal of this study is to examine the effect of neoadjuvant radiochemotherapy on the density of CD8(+) tumor infiltrating lymphocytes (TILs) in endoscopical biopsies and resection specimens from patients with rectal adenocarcinoma before and after therapy. PATIENTS AND METHODS: In total, 53 patients with locally advanced rectal cancer were studied. RESULTS: The median density of CD8(+) TILs in pretreatment biopsies was 12 (1- 232) and that in surgical specimens after radiochemotherapy was 18 (1- 319). During radiochemotherapy, the density of CD8(+) TILs increased in 30 patients (57%), decreased in 18 (34%), and did not change in one. It was not possible to assess the dynamics of CD8(+) TILs density in four patients. The increased density of CD8(+) TILs after radiochemotherapy was associated with a median survival rate 2.5 times longer than that associated with no increase in density. CONCLUSION: In the present study, the density of CD8(+) TILs in endoscopical biopsies before radiochemotherapy, the density in resection specimens after radiochemotherapy, or in changes in the density after radiochemotherapy showed no predictive or prognostic significance. However, studying a larger number of patients may show that CD8(+) TILs density is of predictive or prognostic significance.

[Influence of preoperative chemoradiotherapy on changes of epidermal growth factor receptor expression in patients treated by preoperative chemoradiotherapy for local advanced rectal carcinoma]. / Vliv predoperacní chemoradioterapie na zmenu exprese receptoru pro epidermální rustový faktor u pacientu lécených predoperacní chemoradioterapií pro lokálne pokrocilý karcinom rekta.

AIM: The aim of this retrospective study was to determine the prognostic impact of expression of epidermal growth factor receptor (EGFR) changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal adenocarcinoma. MATERIAL AND METHODS: One hundred and three patients with locally advanced rectal adenocarcinoma of stage II and III were evaluated. All patients were administered the total dose of 44 --  50.4 Gy. Concomitantly, the patients received capecitabine in the dose 825 mg/ m² in two daily oral administrations or 5- fluorouracil in the dose 200 mg/ m² in continuous infusion. Surgery was indicated at intervals of 4-8 weeks from chemoradiotherapy completion. EGFR expression in the pretreatment biopsies and in resected specimens was assessed with immunohistochemistry. RESULTS: All of 103 patients received radiotherapy without interruption up to the total planned dose. Downstaging was described in 64 patients. Six patients had complete pathologic remission. Recurrence occurred in 49 patients. Local recurrence was found in 22 patients, generalization of disease was reported in 27 patients. A total of 51 patients died. Increased EGFR expression was found in 26 patients. The statistically significantly shorter overall survival (p < 0.001) and disease-free survival (p < 0.001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR was observed during neoadjuvant chemoradiotherapy. CONCLUSIONS: The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenocarcinoma is associated with significant shorter overall survival and disease-free survival.

Primary cilia in gastrointestinal stromal tumors.

The primary cilium is a solitary, sensory, non-motile microtubule-based structure that arises from the centrosome and is projected from the surface of most human cells. The objective of the current pilot study was to conduct an investigation of presence and frequency of cilia in gastrointestinal stromal tumors (GIST).The presence of primary cilia in GIST was evaluated in 9 patients, including 8 primary tumors and 1 liver metastasis. In 2 patients the presence of primary cilia was evaluated not only in the primary tumor, but also in recurrence: in 1 patient in recurrence without previous treatment with imatinib and in 1 patient in recurrence after treatment with imatinib. The primary cilia of GIST cells were immunofluorescently stained with primary monoclonal anti-acetylated tubulin alpha antibody and cell nuclei with DAPI.We observed 9985 nuclei of cells of GISTs and 425 primary cilia in total. The median of frequency of primary cilia in cells of GISTs in all examined samples was 4.26%, in primary tumors was 4.32% and in metastases was 3.64%, respectively. This pilot study provides the evidence of the presence of primary cilia in GISTs in different organs. Primary cilia were identified in all examined cases of GIST, including primary tumors, metastases and recurrent lesions without and with previous treatment with imatinib.

[Prognostic significance of changes of tumor epidermal growth factor receptor expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma].

PURPOSE: The aim of the present study was to examine the effect of neoadjuvant chemoradiation on tumor epidermal growth factor receptor (EGFR) expression in patients with locally advanced rectal adenocarcinoma. PATIENTS AND METHODS: A total of 53 patients with rectal adenocarcinoma (clinical stages II and III) were studied. Neoadjuvant treatment consisted of 50.4 Gy/28 fractions external radiation with concomitant continuous 5-fluorouracil. Surgical resection was performed 4-6 weeks after the chemoradiation. EGFR expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry. RESULTS: Patients with an increase of EGFR expression during chemoradiation had significantly shorter disease-free survival (DFS; p = 0.003) and overall survival (OS; p = 0.005) compared to patients with either no change or decrease in EGFR expression. The 5-year DFS in patients with increased EGFR expression was only 29% compared to 61% in patients without an increase of EGFR expression. Similarly, the 5-year OS of the patients with increased EGFR expression was 29% compared to 66% in patients without an increase of EGFR expression. All recurrences in patients who had an increase of EGFR expression occurred within the first 2 years after the treatment. The increase in EGFR expression was the only significant predictor of DFS (p = 0.007) and OS (p = 0.04) using multivariate Cox regression analysis. CONCLUSION: An increase of EGFR expression during chemoradiation may be associated with significantly shorter DFS and OS. The increase of EGFR could identify a population of patients in whom the effect of the treatment with anti-EGFR therapy should be studied.

[Primary cilia of cells of cardiovascular apparatus]. / Primární rasinky bunek kardiovaskulárního aparátu.

The primary cilium is a mechanosensory, solitary, non-motile microtubule-based structure that in the quiescent phase of the cell cycle projects from the surface of the majority of human cells, including embryonal, stem and mesenchymal cells, fibroblasts, myoblasts, cardiomyocytes, vascular smooth muscle and endothelial cells. Primary cilia are in increased frequency also present on the surface of endothelial cells in atherosclerotic predilection sites, lipoid streaks and dots and atheromatous plaques. The primary cilium is formed from the mother centriole. Primary cilia are currently studied in mechanobiology of cardiovascular apparatus and their role in cell migration, cell cycle control and atherogenesis. The aim of this paper is to provide a review of the current knowledge on the primary cilia of cells of cardiovascular apparatus.