The effectiveness of fractionated exposure to gamma- and neutron radiation in their separate and combined use on the growth and functional morphology of mutant p53 sarcoma M-1 in rats was studied. Investigation techniques included immunostaining of PCNA and mutant p53 expressing cells, determination of mitotic activity and apoptotic death of tumor cells, as well as computer analysis of microscopic images. The antitumor efficacy of different types of radiation is shown to be determined by different levels of apoptosis induction, reduced proliferation and cellularity. Neutron radiation of the impulse generator has a marked damaging effect on the vasculature and the development of tumor necrosis. Fractionated irradiation at equal daily doses led to the decrease in the relative effectiveness of radio-inactivation of tumor cells. After 9 fractions of irradiation, the calculated value of the RBE of fast neutrons normalized to the input dose of 1 Gy by the coefficient of tumor growth inhibition, a reduced proliferative activity of PCNA and induced apoptosis of tumor cells was 3.4, 3.7 and 3.1, respectively. In the mode of daily superfractionation with splitting the dose in two fractions, the effectiveness of the combined exposure corresponded to the additive effect of gamma- and neutron radiation with a tendency toward synergism. There are reasons to believe that high resistance of sarcoma M-1 to the ionizing radiation impact is due not only to a fraction of hypoxic cells, but also the mutant status of p53 gene.
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http://dx.doi.org/10.7868/s0869803113020148 | DOI Listing |
Head Neck Pathol
October 2024
Division of Oral and Maxillofacial Pathology, The Ohio State University College of Dentistry, Postle Hall, Room 2191 305 W. 12th Ave, Columbus, OH, 43210, USA.
Bull Exp Biol Med
February 2023
National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia.
We evaluated antitumor efficacy of photodynamic therapy of murine Ehrlich carcinoma and rat sarcoma M-1 with new photosensitizers 13-N-(4-aminobutyl)amydo chlorine e6 (1), 13-(5-guanidylbutanamido)-chlorine e6 (2), and 13-(5-biguanidylbutanamido)-chlorine e6 (3). The inhibiting effect of the photodynamic therapy was evaluated by the following parameters: tumor growth inhibition, complete regression of the tumors, and absolute growth rate of the tumor nodes in animals with the continued neoplasia growth. The criterion of cure was the absence of tumors up to 90 days after the therapy.
View Article and Find Full Text PDFJ Med Chem
January 2023
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
Transcriptional enhanced associate domains (TEADs) are transcription factors that bind to cotranscriptional activators like the yes-associated protein (YAP) or its paralog transcriptional coactivator with a PDZ-binding motif (TAZ). TEAD·YAP/TAZ target genes are involved in tissue and immune homeostasis, organ size control, tumor growth, and metastasis. Here, we report isoindoline and octahydroisoindole small molecules with a cyanamide electrophile that forms a covalent bond with a conserved cysteine in the TEAD palmitate-binding cavity.
View Article and Find Full Text PDFFront Immunol
July 2022
Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, China.
Background: Soft-tissue sarcoma (STS) represents a rare and diverse cohort of solid tumors, and encompasses over 100 various histologic and molecular subtypes. In recent years, RNA modifications including mA, mC, mA, and mG have been demonstrated to regulate immune response and tumorigenesis. Nevertheless, the cross-talk among these RNA modification regulators and related effects upon the tumor microenvironment (TME), immune infiltrates, and immunotherapy in STS remain poorly understood.
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