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 expression of immunohistochemical tumor markers Ki-67, b-catenin, Bcl-2, P53, connexin 32 and connexin 43 when using 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in mice with xenographs of squamous cell lung cancer.Materials and methods. Subcutaneous PDX models of human squamous cell lung cancer were created in immunodeficient BALB/c Nude mice. A fragment of the patient’s tumor (3 × 3 × 3 mm) was implanted subcutaneously in the right thigh of a previously anesthetized mouse. 200 μl of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone was administered orally using a probe in 12 doses once every 3 days. All animals were divided into groups depending on the tropolone doses: experimental groups 2–5 with doses of 0.0055, 0.055, 0.55 and 2.75 mg/g, respectively. The control group received 1 % starch gel which was tropolone carrier. The animals were euthanized 36 days after the start of the substance administration, and the tumor tissue was isolated and prepared for the IHC study according to the standard protocol. IHC reactions were performed using antibodies for Ki-67, b-catenin, Bcl-2, P53, connexin 32 and connexin 43.Results. Higher tropolone doses were associated with decreased expression of Ki-67, b-catenin, and the Bcl-2 protein, but increased expression of the P53 protein. The dosage of tropolone and expression of connexin 43 were directly proportional.Conclusion. Immunohistochemical analysis of expression of proteins in PDX models of human squamous cell lung cancer when using 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone showed the changes indicating its antitumor efficacy and suggesting a possible mechanism of action based on the activation of apoptosis.
Glioblastoma (GBM) is the most malignant and the most common primary tumor of the central nervous system. During the last several years GBM has been classified and managed according to the World Health Organization (WHO) criteria which subdivide it into primary and secondary GBM. As it is suggested, GBM originates from glial cells and has a diffuse growth pattern, but its etiology and pathophysiology are poorly investigated up to date. Its rapid progression and anatomical location in the brain often limits the effectiveness of therapeutic interventions. Despite all scientific and technological advances, GBM remains an incurable disease with a median survival of approximately 18 months. Standard treatment options involving maximal safe resection of the tumor followed with radiotherapy and chemotherapy do not provide satisfactory Results.Better understanding of the molecular pathology of GBM and its associated signaling pathways has opened up possibilities for new treatments for newly diagnosed and relapsing tumors. A multitargeted therapeutic approach using compounds capable of inhibiting more than one specific molecular target is a promising alternative to conventional therapies.Currently, specialists study such innovative treatment options as small molecule inhibitors aimed at signaling pathway disruptions, immunotherapy, including checkpoint inhibitors, oncolytic vaccines, CAR T-cell therapy, and drug delivery systems. In terms of an innovative approach, the elaboration of targeted drug delivery systems is of particular interest, since this strategy looks the most promising due to its ability to increase the bioavailability and effectiveness of both standard and newly tested agents. This review discusses results of preclinical and clinical studies of innovative therapeutic approaches, their advantages and disadvantages. An interdisciplinary approach is expected to be able to combine the results of cutting-edge research in this area and to provide novel promising therapeutic strategies for patients with GBM.
Эксперименты с использованием лабораторных животных необходимы для лучшего понимания течения той или иной патологии, изучения механизмов ее развития и разработки новых терапевтических стратегий. Значительная часть экспериментальных исследований требует выполнения процедуры анестезии. В связи с этим выбор оптимального протокола по анестезии является важным пунктом исследований, так как недостаточная глубина наркоза и влияние нежелательных факторов на организм объекта могут привести к летальному исходу. Для нас представляло интерес выяснить, что поменялось в области анестезии лабораторных животных за последнее время, какие препараты актуальны на данный момент и в чем причина их популярности. Анестезия мышей является сложной задачей по нескольким причинам: размер животного, скорость метаболизма и высокий риск гипотермии и гипогликемии. Кроме того, анестетики действуют на физиологические параметры, что еще больше влияет на результаты экспериментов. На данный момент существует большой перечень препаратов, применяемых на лабораторных животных. Поскольку они подразделяются на группы в зависимости от путей введения, из ряда статей мы отобрали следующие препарата: инъекционные -«Медетомидин», «Дексмедетомидин», «Золетил-100», «Кетамин», «Ксила», «Пропофол» и ингаляционные -«Изофлуран», «Севофлуран». Изучили и описали преимущества и недостатки препаратов и их сочетаний. Согласно анализу литературных источников, инъекционная анестезия считается основным методом наркоза для экспериментальных животных и сравнительно хорошо переносится животными, так же не требует дополнительной громоздкой аппаратуры, дополнительной квалификации сотрудников, на ряд препаратов существуют антагонисты, имеет доступную стоимость. При длительных сложных манипуляциях/операциях в большинстве литературы использовали ингаляционный наркоз, так как он более управляем, агенты требуют минимального метаболизма, в ряде случаев не требует дополнительной седации.
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