Purpose of the study. The investigation is aimed to provide a systematic comparison of different contrasting methods for in vivo micro-CT diagnostic of orthotopic colorectal cancer models extracted by ortotopic implantation into the caecum of immunocompromised mice BALB/c Nude lines.Materials and methods. BALB/c Nude (N = 25) female mice were implanted by transplanted human colorectal cancer strain into the cecum. 20 days after the implantation mice were administered with iodine-based contrast agent Optiray by means of different administration method (intravenously, per os, intraperitoneally, per rectum) and micro-CT scans have been registered via Quantum GX2 tomograph. Measurement of tumor nodes was performed both by means of estimation from micro-CT images via RadiAnt DICOM Viewer software and by means of explicit measurements using calipers upon laparotomy and posthumously. At the last stage of the study, the animals were euthanized by cervical dislocation. The tumors were excised, measured with a caliper and placed in 10 % formalin for the standard histological analysis according to the standard methods.Results. The average volumes of tumor xenografts in animals with intravenous, oral, and intraperitoneal contrast administration measured at micro-CT were 53.7 ± 5.2 mm3, 52.7 ± 6.4 mm3 and 63.6 ± 5.6 mm3 respectively; measured at laparotomy – 43.0 ± 5.5 mm3, 44.5 ± 5.4 mm3 and 58.5 ± 5.5 mm3 respectively; measured post-mortem – 55.2 ± 6.6 mm3, 53.2 ± 8.8 mm3 and 65.9 ± 3.8 mm3 respectively. The average volumes of tumor xenografts isolated post-mortem in these groups were comparable with the values shown at micro-CT, but larger than the volumes measured at laparotomy.Conclusion. The results obtained demonstrated that intravenous, peroral and intraperitoneal administration techniques provide the best visualization of laboratory rodents pathological tissue upon in vivo micro-CT diagnostics and thus are preferred.
Purpose of the study. Evaluation of the antioxidant status and DNA damage in tissues of subcutaneous xenografts of non-small cell lung cancer and in peritumoral tissues created using the A549 and H1299 cell cultures.Materials and methods. The study included 35 intact male Balb/c Nude immunodeficient mice. Cell lines A549 and H1299 were used as transplantable tumor biomaterial. A CDX model was created in accordance with the protocol for supratentorial injections (Ozawa T., James C. D., 2010) adapted for this experiment. Growth rates were controlled and intracranial xenografts were visualized using a high-resolution micro-CT system. The activity of catalase and superoxide dismutase was determined with non-denaturing electrophoresis in 8 % and 12 % polyacrylamide gel. The concentrations of sulfhydryl groups were determined according to Ellman. The DNA damage in lymphocytes was determined by the comet assay.Results. The experiment resulted in the creation of models of brain tumors characterized by intracranial growth pattern in 100 %. The activity of catalase in the studied lysates of intracranial xenografts, peritumoral tissue and healthy tissues of tumor-bearing animals in all experimental groups increased statistically significantly relative to the healthy tissue of intact animals, and the greatest differences from the control were recorded in the group of animals with implanted H1299 culture at a concentration of 1 × 106 . Superoxide dismutase activity in the studied lysates of intracranial xenografts and peritumoral tissues statistically significantly increased compared to the control sample in all experimental groups. The highest increase in the SOD activity was observed in the tissues of intracranial xenografts with the highest tumor load, which amounted to 28.8 % and 32.9 % of the changes relative to the control sample. A statistically significant increase in the concentration of SH-groups relative to the control sample in tumor tissue lysates was revealed in all experimental groups, and the highest concentration (36.2 ± 0.47) was observed in the group of experimental animals with the highest tumor load. Percentage change in tail moment (DNA damage indicator) in groups O1, O2, O3 and O4 increased statistically significantly compared to the control sample by 55.8 %, 111.8 %, 97.3 % and 170 %, respectively.Conclusions. The observed increase in the activity of the antioxidant defense system, accumulation of oxidative modifications of proteins, and an increase in DNA double-strand breaks in the tissues of intracranial xenografts of non-small cell lung cancer in vivo suggest that the created models reflect processes similar to those in tumors of human non-small cell lung cancer.
This article reviews modern ideas about the pathogenesis of chronic pain in cancer patients and describes main approaches to its relief. Special attention is focused on factors important for the development of a patient-specific approach to the pathophysiology and management of chronic pain syndrome. These factors include genetics, gender, age, early anamnesis, patients’ immunological and endocrine status, as well as those shedding light on the pathogenetic aspects of chronic pain thus facilitating the choice of an optimal therapeutic approach. The review identifies limitations of pharmacotherapy as the major method of chronic pain management and justifies the need for alternative approaches. The latter include monitoring of the circadian rhythms of pain and various nonspecific effects, such as physical factors, psychological methods or reflex therapy. The experience and possibilities of non–pharmacological methods in the complex pathogenetic therapy of chronic pain are analysed, along with preventive measures permitting the development of chronic pain to be avoided. The pathological disorganizing and stressful role of chronic pain is considered with regard to the theory of functional systems. The pathogenetic significance of chronic pain in carcinogenesis and cancer progression is illustrated by examples from scientific literature. The authors emphasize the necessity of effective pain prevention, including invasive methods, in order to ensure an acceptable quality of life for cancer patients at any stage of the malignant process.
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