title: ÐÐ¾Ð¼Ð¿Ð»ÐµÐºÑÐ½Ð¾Ðµ Ð²Ð¾Ð·Ð´ÐµÐ¹ÑÑÐ²Ð¸Ðµ Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾ÑÐ° ÑÐ¸Ð³Ð½Ð°Ð»ÑÐ½Ð¾Ð³Ð¾ Ð¿ÑÑÐ¸ Sonic Hedgehog Ð¸ Ð¸Ð¾Ð½Ð¸Ð·Ð¸ÑÑÑÑÐµÐ³Ð¾ Ð¸Ð·Ð»ÑÑÐµÐ½Ð¸Ñ Ð½Ð° Ð¾Ð¿ÑÑ Ð¾Ð»ÐµÐ²ÑÐµ ÐºÐ»ÐµÑÐºÐ¸ Ð³Ð»Ð¸Ð¾Ð¼
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¼Ð°Ð³Ð¸ÑÑÑÐ°
titleType: Subtitle
title: The complex effect of the inhibitor of the Sonic Hedgehog signaling pathway and ionizing radiation on glioma tumor cells
Creators: name: ÐÐ°ÑÐ¸Ð½Ð°, ÐÐ»Ð¸Ð½Ð°
Publisher: name: Ð¡Ð°Ð½ÐºÑ-ÐÐµÑÐµÑÐ±ÑÑÐ³ÑÐºÐ¸Ð¹ Ð¿Ð¾Ð»Ð¸ÑÐµÑÐ½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÐ½Ð¸Ð²ÐµÑÑÐ¸ÑÐµÑ ÐÐµÑÑÐ° ÐÐµÐ»Ð¸ÐºÐ¾Ð³Ð¾
Year: 2023
Subjects: Ð³Ð»Ð¸Ð¾Ð¼Ñ
Sonic Hedgehog
Ð¿ÑÐ¾ÑÐ¾Ð½Ð½Ð°Ñ ÑÐµÑÐ°Ð¿Ð¸Ñ
Ð»ÑÑÐµÐ²Ð°Ñ ÑÐµÑÐ°Ð¿Ð¸Ñ
GANT61
Ð³Ð°Ð¼Ð¼Ð°-Ð¸Ð·Ð»ÑÑÐµÐ½Ð¸Ðµ
gliomas
proton therapy
radiation therapy
gamma irradiation

description: ÐÐ°Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° Ð¸Ð·ÑÑÐµÐ½Ð¸Ñ ÑÐ°Ð´Ð¸Ð¾ÑÐµÐ½ÑÐ¸Ð±Ð¸Ð»Ð¸Ð·Ð¸ÑÑÑÑÐµÐ³Ð¾ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»Ð° Ð¿ÑÐµÐ¿Ð°ÑÐ°ÑÐ° GANT61, Ð´Ð¾Ð±Ð°Ð²Ð»ÐµÐ½Ð½Ð¾Ð³Ð¾ Ðº ÐºÐ»ÐµÑÐºÐ°Ð¼ Ð³Ð»Ð¸Ð¾Ð¼ Ð´Ð¾ Ð¸Ð»Ð¸ Ð¿Ð¾ÑÐ»Ðµ Ð¾Ð±Ð»ÑÑÐµÐ½Ð¸Ñ, Ð° ÑÐ°ÐºÐ¶Ðµ ÑÑÐ°Ð²Ð½ÐµÐ½Ð¸Ñ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»ÑÐ½Ð¾Ð¹ ÑÐ°Ð·Ð½Ð¸ÑÑ Ð¼ÐµÐ¶Ð´Ñ ÐºÐ¾Ð¼Ð¿Ð»ÐµÐºÑÐ½ÑÐ¼ Ð´ÐµÐ¹ÑÑÐ²Ð¸ÐµÐ¼ Ð¿ÑÐµÐ¿Ð°ÑÐ°ÑÐ° Ð¸ Ð¿ÑÐ¾ÑÐ¾Ð½Ð½ÑÐ¼ Ð¸Ð»Ð¸ Ð³Ð°Ð¼Ð¼Ð°-Ð¾Ð±Ð»ÑÑÐµÐ½Ð¸ÐµÐ¼. ÐÐ»Ð¸Ð¾Ð¼Ñ â ÑÑÐ¾ Ð±ÑÑÑÑÐ¾ Ð¿ÑÐ¾Ð³ÑÐµÑÑÐ¸ÑÑÑÑÐ¸Ðµ Ð¾Ð¿ÑÑÐ¾Ð»Ð¸ Ð³Ð¾Ð»Ð¾Ð²Ð½Ð¾Ð³Ð¾ Ð¼Ð¾Ð·Ð³Ð°, Ð¿Ð»Ð¾ÑÐ¾ Ð¿Ð¾Ð´Ð´Ð°ÑÑÐ¸ÐµÑÑ ÑÑÐ°Ð½Ð´Ð°ÑÑÐ½Ð¾Ð¹ ÑÐµÑÐ°Ð¿Ð¸Ð¸. ÐÐ»Ð¾ÐºÐ°ÑÐµÑÑÐ²ÐµÐ½Ð½Ð°Ñ ÑÑÐ°Ð½ÑÑÐ¾ÑÐ¼Ð°ÑÐ¸Ñ ÑÐ²ÑÐ·Ð°Ð½Ð° Ñ Ð¿Ð¾ÑÐµÑÐµÐ¹ ÐºÐ»ÐµÑÐ¾ÑÐ½Ð¾Ð¹ Ð´Ð¸ÑÑÐµÑÐµÐ½ÑÐ¸ÑÐ¾Ð²ÐºÐ¸. ÐÐ¾ÐºÐ°Ð·Ð°Ð½Ð¾, ÑÑÐ¾ ÑÐ¸Ð³Ð½Ð°Ð»ÑÐ½ÑÐ¹ Ð¿ÑÑÑ Sonic Hedgehog ÑÐ²Ð»ÑÐµÑÑÑ Ð¾Ð´Ð½Ð¸Ð¼ Ð¸Ð· Ð¼ÐµÑÐ°Ð½Ð¸Ð·Ð¼Ð¾Ð², Ð¿Ð¾Ð´Ð´ÐµÑÐ¶Ð¸Ð²Ð°ÑÑÐ¸Ñ ÐºÐ»ÐµÑÐºÐ¸ Ð² ÑÐ¾ÑÑÐ¾ÑÐ½Ð¸Ð¸ Ð¿Ð¾ÑÐ¾Ð¶ÐµÐ¼ Ð½Ð° ÑÐ¾, Ð² ÐºÐ¾ÑÐ¾ÑÐ¾Ð¼ Ð½Ð°ÑÐ¾Ð´ÑÑÑÑ ÑÑÐ²Ð¾Ð»Ð¾Ð²ÑÐµ ÐºÐ»ÐµÑÐºÐ¸. ÐÐ¾ÑÑÐ¾Ð¼Ñ ÑÐ°ÑÑÐµÑ Ð¸Ð½ÑÐµÑÐµÑ Ðº Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ñ Ð¿ÑÑÐ¸ Sonic Hedgehog Ð² ÑÐ¾ÑÐµÑÐ°Ð½Ð¸Ð¸ Ñ Ð»ÑÑÐµÐ²Ð¾Ð¹ ÑÐµÑÐ°Ð¿Ð¸ÐµÐ¹. ÐÐ°Ð¼Ð¸ Ð±ÑÐ» Ð²ÑÐ±ÑÐ°Ð½ Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾Ñ GANT61, ÐºÐ¾ÑÐ¾ÑÑÐ¹ ÑÐ²ÑÐ·ÑÐ²Ð°ÐµÑÑÑ Ñ ÑÑÐ°Ð½ÑÐºÑÐ¸Ð¿ÑÐ¸Ð¾Ð½Ð½ÑÐ¼Ð¸ ÑÐ°ÐºÑÐ¾ÑÐ°Ð¼Ð¸ Gli1, ÑÑÐ¾ Ð¿ÑÐµÐ¿ÑÑÑÑÐ²ÑÐµÑ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ Sonic Hedgehog. ÐÐ¿ÑÑÐ¾Ð»ÐµÐ²ÑÐµ ÐºÐ»ÐµÑÐºÐ¸ Ð¿ÑÐµÐ´Ð²Ð°ÑÐ¸ÑÐµÐ»ÑÐ½Ð¾ Ð¸Ð½ÐºÑÐ±Ð¸ÑÐ¾Ð²Ð°Ð»Ð¸ Ñ GANT61 Ð¸ Ð¾Ð±Ð»ÑÑÐ°Ð»Ð¸ Ð³ÑÐ°Ð´ÑÐ¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÐ¼Ð¸ Ð´Ð¾Ð·Ð°Ð¼Ð¸ 0,5-6 ÐÑ Ð¿ÑÐ¾ÑÐ¾Ð½Ð°Ð¼Ð¸ Ð½Ð° Ð¿Ð¸ÐºÐµ ÐÑÑÐ³Ð³Ð° Ð½Ð° ÑÐ¸Ð½ÑÑÐ¾ÑÐ¸ÐºÐ»Ð¾ÑÑÐ¾Ð½Ðµ Ð¡Ð¦-1000 (ÑÐ½ÐµÑÐ³Ð¸Ñ: 200 ÐÑÐ), Ð° ÑÐ°ÐºÐ¶Ðµ Ð´Ð¾Ð·Ð°Ð¼Ð¸ 2-6 ÐÑÐµÐ¹ Ñ Ð¸ÑÐ¿Ð¾Ð»ÑÐ·Ð¾Ð²Ð°Ð½Ð¸ÐµÐ¼ 60Co Ð¸ÑÑÐ¾ÑÐ½Ð¸ÐºÐ° Î³-Ð»ÑÑÐµÐ¹ "ÐÑÑÐ»ÐµÐ´Ð¾Ð²Ð°ÑÐµÐ»Ñ". Ð Ð´ÑÑÐ³Ð¾Ð¹ Ð³ÑÑÐ¿Ð¿Ðµ ÑÐºÑÐ¿ÐµÑÐ¸Ð¼ÐµÐ½ÑÐ¾Ð² Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾Ñ Ð´Ð¾Ð±Ð°Ð²Ð»ÑÐ»Ð¸ Ð¿Ð¾ÑÐ»Ðµ Ð¾Ð±Ð»ÑÑÐµÐ½Ð¸Ñ. Ð§ÑÐ²ÑÑÐ²Ð¸ÑÐµÐ»ÑÐ½Ð¾ÑÑÑ Ðº Ð¸Ð·Ð»ÑÑÐµÐ½Ð¸Ñ Ð¾Ð¿ÑÐµÐ´ÐµÐ»ÑÐ»Ð¸ Ñ Ð¿Ð¾Ð¼Ð¾ÑÑÑ MTS-ÑÐµÑÑÐ° Ð¸ Ð°Ð½Ð°Ð»Ð¸Ð·Ð° ÐºÐ¾Ð»Ð¾Ð½Ð¸Ð¹. ÐÐ¾ ÑÐµÐ·ÑÐ»ÑÑÐ°ÑÐ°Ð¼ ÑÐ°Ð±Ð¾ÑÑ Ð¼Ñ Ð¼Ð¾Ð¶ÐµÐ¼ ÑÐ´ÐµÐ»Ð°ÑÑ Ð²ÑÐ²Ð¾Ð´, ÑÑÐ¾ GANT61 Ð¼Ð¾Ð¶ÐµÑ Ð±ÑÑÑ Ð¿ÑÐµÐ¿Ð°ÑÐ°ÑÐ¾Ð¼, Ð¸ÑÐ¿Ð¾Ð»ÑÐ·Ð¾Ð²Ð°Ð½Ð½ÑÐ¼ Ð² ÑÐ¸Ð¼Ð¸Ð¾ÑÐµÑÐ°Ð¿Ð¸Ð¸ Ð³Ð»Ð¸Ð¾Ð¼, ÐºÐ¾Ð¼Ð±Ð¸Ð½Ð¸ÑÐ¾Ð²Ð°Ð½Ð½Ð¾Ð¹ Ñ Ð»ÑÑÐµÐ²Ð¾Ð¹ ÑÐµÑÐ°Ð¿Ð¸ÐµÐ¹. ÐÐ´Ð½Ð°ÐºÐ¾, ÑÑÑÐµÐºÑ, Ð¿Ð¾-Ð²Ð¸Ð´Ð¸Ð¼Ð¾Ð¼Ñ, Ð·Ð°Ð²Ð¸ÑÐ¸Ñ Ð¾Ñ Ð±Ð¸Ð¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸Ñ Ð¾ÑÐ¾Ð±ÐµÐ½Ð½Ð¾ÑÑÐµÐ¹ ÐºÐ»ÐµÑÐ¾ÑÐ½ÑÑ ÐºÑÐ»ÑÑÑÑ.
description: The given work is devoted to the study of the radiosensitizing potential of the drug GANT61 added to glioma cells before or after irradiation, as well as comparing the difference between the complex effect of the drug and proton or gamma irradiation. Gliomas are rapidly progressing brain tumors that do not respond well to standard therapy. Malignant transformation is associated with the loss of cell differentiation. It has been shown that the Sonic Hedgehog signaling pathway is one of the mechanisms that supports cells in a state similar state of stem cells. Therefore, there is growing interest in inhibiting the Sonic Hedgehog pathway in combination with radiation therapy. We selected an inhibitor GANT61, which binds to transcription factors Gli1, which prevents the activity of Sonic Hedgehog. Tumor cells were pre-incubated with GANT61 and irradiated with graduated doses of 0.5-6 Gy of Bragg peak of proton beam on the synchrocyclotron SC-1000 (energy: 200 MeV), as well as doses of 2-6 Gray on a 60Co gamma-ray source "Researcher". In another group of experiments, an inhibitor was added after irradiation. Sensitivity to radiation was determined using the MTS test and colony analysis. Based on the results of the work, we can say that GANT61 can be a drug used in glioma chemotherapy combined with radiation therapy. However, the effect seems to depend on the biological characteristics of cell cultures.