Evaluation of the chicken embryo chorioallantoic membrane model for laryngeal tumor transplantation

The laryngeal squamous cell carcinoma is the second common malignant tumor of the respiratory tract and together with recurrent respiratory papillomas represents the most common tumors of the larynx. Many experimental models are used to study the morphology of malignant tumors. The chicken chorioallantoic membrane (CAM) model is one of them. The CAM has all the nutrition needed for the piece of the transplanted tumor to survive. The aim of this study was to investigate whether the laryngeal papilloma and the laryngeal squamous cell carcinoma tissues transplanted on the chick CAM survive with their main histological features, and to determine the morphological changes of the CAM with different transplants. For the preparation of the CAM, fertilized hen eggs were put into an incubator for 3 days. Then the windows in the shell were opened. The fresh samples of tumors were transplanted on the CAM on the 7th day of incubation. After 3 days after transplantation the CAM with onplants were excised and fixed in the 10% formalin solution. Morphological changes in the control CAM and in the CAM with tumor onplants were observed using the digital camera on the OLYMPUS microscope. The results showed that the CAM with the laryngeal squamous cell carcinoma onplant was distinctly thicker than that of the control group and than the CAM with the papilloma onplant; the chorionic epithelium was thickened and appeared stratified of up to 5–6 layers and in some locations squamous keratinized; the mesenchymal cells were densely arranged under the tumor transplants. We observed that morphological changes in the thickness of the CAM and the chorionic epithelium were more obvious in the CAM under the carcinoma transplants. After 72 hours of the tumor tissue transfer onto the membrane, the tumor cells retained their vitality and also their influence on the CAM tissues could be observed

Changes of the chicken chorioallantoic membrane and the behaviour of transplanted glioblastoma

Glioblastoma is the most common brain malignancy and is marked by an extremely poor prognosis, despite advances in surgical and clinical neuro-oncology. Glioblastomas are very heterogenic in their biological and morphological features and they are widely investigated. Existing in vivo glioblastoma models are based on the inoculation of glioma cells or cell lines into the rodent brain, the dog brain or the use of transgenic mice causing spontaneous tumors. These models suffer from the variable growth rate and poor penetration, and are limited by the difficulty of obtaining morphological data. In our research we suggested the model in which the native human glioblastoma was transplanted into the chicken embryo chorioallantoic membrane. The glioblastoma was transplanted into the embryo's chorioallantoic membrane on the seventh–ninth day, when it was fully developed and could ensure the nutrition of the tumor. Transplantation was successful if the glioblastoma survived at least for 24 hours together with the embryo. The chorioallantoic membrane after transplantation showed thickening. Between 48 and 120 hours after transplantation the thickness of the membrane changed from 2x to 5x. Starting from 144 hours after transplantation the thickness of the membrane diminished. The tumor transplanted into the chorioallantoic membrane ingrows in it in the zones where the epithelium of the membrane was mechanically removed. The tumor keeps its proliferative activity until 48 hours of transplantation, afterwards the proliferative activity is noticed in the chorioallantoic membrane until 120 hours of transplantation. This shows that the main processes take place in the zone where the tumor adheres to the chorioallantoic membrane. The human glioblastoma transplanted on chicken chorioallantoic membrane repeated all the essential stages of tumor growth, which are also typical of other mammal models. This model reflects the morphological and biological features of the glioblastoma, allows to evaluate the invasivity, the progress of the tumor, and to investigate new medicines

Age related structural changes in human basilar artery

The basilar artery is the most important artery in the posterior cerebral circulation. In the cases of stroke due to acute basilar artery occlusion the mortality rate is significantly higher if compared to all the stroke cases. Arterial wall stiffening is characteristic of ageing arteries and in many investigations arterial wall stiffening is related to the loss of the elastic component in the arterial wall during ageing. In arterial stiffening the changes in the collagen content and the number of smooth muscle cells (SMC) may also play a role. Basilar arteries were obtained within 24 hours postmortem from 89 human cadavers (44 male and 45 female). From the middle part of the basilar arteries histological slides were performed and area of collagen fibers, the number of smooth muscle cells and the thickness of the media were measured. The morphometric analysis revealed the increase of collagen network area with the age. Analysing age-related changes in the number of SMC in male and female basilar artery media, we determined that in both genders the number of SMC in the media decreased. Changes in SMC number in both genders had a strong negative correlation with the age (r=–0.93 in the male group and r=–0.95 in the female group, respectively). In the analysis of the media thickness in different gender and age groups, its thickening was determined. The correlation with the age was of medium strength both in the male (r=0.36) and female (r=0.4) group. In all the cases this correlation was statistically significant (p<0.05). Our morphometric findings that revealed the increased collagen area together with the decrease of the SMC number might be responsible for the stiffening of the basilar artery in aging and contribute to the development of atherosclerosis and arterial hypertension

The importance of gender-related anticancer research on mitochondrial regulator sodium dichloroacetate in preclinical studies in vivo

Sodium dichloroacetate (DCA) is an investigational medicinal product which has a potential anticancer preparation as a metabolic regulator in cancer cells’ mitochondria. Inhibition of pyruvate dehydrogenase kinases by DCA keeps the pyruvate dehydrogenase complex in the active form, resulting in decreased lactic acid in the tumor microenvironment. This literature review displays the preclinical research data on DCA’s effects on the cell pyruvate dehydrogenase deficiency, pyruvate mitochondrial oxidative phosphorylation, reactive oxygen species generation, and the Na+–K+–2Cl− cotransporter expression regulation in relation to gender. It presents DCA pharmacokinetics and the hepatocarcinogenic effect, and the safety data covers the DCA monotherapy efficacy for various human cancer xenografts in vivo in male and female animals. Preclinical cancer researchers report the synergistic effects of DCA combined with different drugs on cancer by reversing resistance to chemotherapy and promoting cell apoptosis. Researchers note that female and male animals differ in the mechanisms of cancerogenesis but often ignore studying DCA’s effects in relation to gender. Preclinical gender-related differences in DCA pharmacology, pharmacological mechanisms, and the elucidation of treatment efficacy in gonad hormone dependency could be relevant for individualized therapy approaches so that gender-related differences in treatment response and safety can be proposed

The importance of gender-related anticancer research on mitochondrial regulator sodium dichloroacetate in preclinical studies in vivo

Sodium dichloroacetate (DCA) is an investigational medicinal product which has a potential anticancer preparation as a metabolic regulator in cancer cells’ mitochondria. Inhibition of pyruvate dehydrogenase kinases by DCA keeps the pyruvate dehydrogenase complex in the active form, resulting in decreased lactic acid in the tumor microenvironment. This literature review displays the preclinical research data on DCA’s effects on the cell pyruvate dehydrogenase deficiency, pyruvate mitochondrial oxidative phosphorylation, reactive oxygen species generation, and the Na+–K+–2Cl− cotransporter expression regulation in relation to gender. It presents DCA pharmacokinetics and the hepatocarcinogenic effect, and the safety data covers the DCA monotherapy efficacy for various human cancer xenografts in vivo in male and female animals. Preclinical cancer researchers report the synergistic effects of DCA combined with different drugs on cancer by reversing resistance to chemotherapy and promoting cell apoptosis. Researchers note that female and male animals differ in the mechanisms of cancerogenesis but often ignore studying DCA’s effects in relation to gender. Preclinical gender-related differences in DCA pharmacology, pharmacological mechanisms, and the elucidation of treatment efficacy in gonad hormone dependency could be relevant for individualized therapy approaches so that gender-related differences in treatment response and safety can be proposed