Effects of p53 Status of Tumor Cells and Combined Treatment With Mild Hyperthermia, Wortmannin or Caffeine on Recovery From Radiation-Induced Damage

Unsatisfactory results of complex treatment for malignant brain tumors stimulate search of new effective methods of treatment. Radiation therapy is an integral part of the combined treatment but often does not influence lethally on resistant tumor cells. Thereby in recent decades there has been an active search for different modifiers, which can increase the sensitivity of tumors to chemotherapy and radiotherapy. One of the universal sensitizers is the local hyperthermia. Experimental data showed that the effect of high temperatures had both a direct damaging effect on tumor cells and a sensitizing effect. The literature review given in the article provides an overview of the existing methods of the local hyperthermia for brain tumors treatment.

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Tumor cells suppress radiation-induced immunity by hijacking caspase 9 signaling

Nature Immunology ◽

10.1038/s41590-020-0641-5 ◽

2020 ◽

Vol 21 (5) ◽

pp. 546-554 ◽

Cited By ~ 13

Author(s):

Chuanhui Han ◽

Zhida Liu ◽

Yunjia Zhang ◽

Aijun Shen ◽

Chunbo Dong ◽

...

Keyword(s):

Tumor Cells ◽

Caspase 9 ◽

Radiation Induced ◽

Induced Immunity

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Octreotide and Pasireotide Combination Treatment in Somatotroph Tumor Cells: Predominant Role of SST2 in Mediating Ligand Effects

Cancers ◽

10.3390/cancers13081816 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1816

Author(s):

Jessica Amarù ◽

Federica Barbieri ◽

Marica Arvigo ◽

Agnese Solari ◽

Adriana Bajetto ◽

...

Keyword(s):

Cell Proliferation ◽

Tumor Cells ◽

Intracellular Signaling ◽

Somatostatin Receptor ◽

Combined Treatment ◽

Primary Cultures ◽

Receptor Subtype ◽

Camp Accumulation ◽

Gh Secretion ◽

Somatostatin Receptor Ligands

First-generation somatostatin receptor ligands (fg-SRLs), such as octreotide (OCT), represent the first-line medical therapy in acromegaly. Fg-SRLs show a preferential binding affinity for somatostatin receptor subtype-2 (SST2), while the second-generation ligand, pasireotide (PAS), has high affinity for multiple SSTs (SST5 > SST2 > SST3 > SST1). Whether PAS acts via SST2 in somatotroph tumors, or through other SSTs (e.g., SST5), is a matter of debate. In this light, the combined treatment OCT+PAS could result in additive/synergistic effects. We evaluated the efficacy of OCT and PAS (alone and in combination) on growth hormone (GH) secretion in primary cultures from human somatotroph tumors, as well as on cell proliferation, intracellular signaling and receptor trafficking in the rat GH4C1 cell line. The results confirmed the superimposable efficacy of OCT and PAS in reducing GH secretion (primary cultures), cell proliferation, cAMP accumulation and intracellular [Ca2+] increase (GH4C1 cells), without any additive effect observed for OCT+PAS. In GH4C1 cells, co-incubation with a SST2-selective antagonist reversed the inhibitory effect of OCT and PAS on cell proliferation and cAMP accumulation, while both compounds resulted in a robust internalization of SST2 (but not SST5). In conclusion, OCT and PAS seem to act mainly through SST2 in somatotroph tumor cells in vitro, without inducing any additive/synergistic effect when tested in combination.

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Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells

Nanomaterials ◽

10.3390/nano11051298 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1298

Author(s):

Vicente Candela-Noguera ◽

Gema Vivo-Llorca ◽

Borja Díaz de Greñu ◽

María Alfonso ◽

Elena Aznar ◽

...

Keyword(s):

Cell Death ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Tumor Cells ◽

Mesoporous Silica Nanoparticles ◽

Combined Treatment ◽

Bond Rupture ◽

Enzyme Prodrug Therapy ◽

Bacterial Gene ◽

Reducing Environment

We report herein a gene-directed enzyme prodrug therapy (GDEPT) system using gated mesoporous silica nanoparticles (MSNs) in an attempt to combine the reduction of side effects characteristic of GDEPT with improved pharmacokinetics promoted by gated MSNs. The system consists of the transfection of cancer cells with a plasmid controlled by the cytomegalovirus promoter, which promotes β-galactosidase (β-gal) expression from the bacterial gene lacZ (CMV-lacZ). Moreover, dendrimer-like mesoporous silica nanoparticles (DMSNs) are loaded with the prodrug doxorubicin modified with a galactose unit through a self-immolative group (DOXO-Gal) and modified with a disulfide-containing polyethyleneglycol gatekeeper. Once in tumor cells, the reducing environment induces disulfide bond rupture in the gatekeeper with the subsequent DOXO-Gal delivery, which is enzymatically converted by β-gal into the cytotoxic doxorubicin drug, causing cell death. The combined treatment of the pair enzyme/DMSNs-prodrug are more effective in killing cells than the free prodrug DOXO-Gal alone in cells transfected with β-gal.

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CBIO-11. NOVEL THERAPY TO TARGET PR-RECURRENT GLIOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.071 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii17-ii18

Author(s):

Masum Rahman ◽

Ian E Olson ◽

Rehan Saber ◽

Jibo Zhang ◽

Lucas P Carlstrom ◽

...

Keyword(s):

Tumor Cells ◽

Tumor Recurrence ◽

Primary Brain Tumor ◽

Differential Sensitivity ◽

Proliferating Cells ◽

Novel Therapy ◽

Conventional Radiation ◽

Long Time ◽

Radiation Induced

Abstract BACKGROUND Glioblastoma is a fatal infiltrative primary brain tumor, and standard care includes maximal safe surgical resection followed by radiation and Temozolomide (TMZ). Therapy-resistant residual cells persist in a latent state a long time before inevitable recurrence. Conventional radiation and Temozolomide (TMZ) treatment cause oxidative stress and DNA damage resulting senescent-like state of cell-cycle arrest. However, increasing evidence demonstrates escaping senescence leads to tumor recurrence. Thus, the ablation of senescent tumor cells after chemoradiation may be an avenue to limit tumor recurrence. METHODS 100uM TMZ for 7days or 10-20Gy radiation (cesium gamma radiator) was used for senescence induction in human glioblastoma in vitro and confirmed by SA-Beta gal staining and PCR. Replication arrest assessed by automated quantification of cellular confluence (Thermo Scientific Series 8000 WJ Incubator). We evaluated the IC50 for several senolytics targeting multiple SCAPs, including Dasatinib, Quercetin, AMG-232, Fisetin, Onalespib, Navitoclax, and A1331852, and in senescent vs. proliferating cells. RESULTS Among the senolytic tested, the Bcl-XL inhibitors A1331852 and Navitoclax both shown senolytic effect by selectively killing radiated, senescent tumor cells at lower concentrations as compared to 0Gy treated non-senescent cells. Across 12 GBM cell lines, IC50 for senescent cells was 6–500 times lower than non-senescent GBM(p< 0.005). Such differential sensitivity to Bcl-XL inhibition after radiation has also observed by BCL-XL knockdown in radiated glioma. CONCLUSION These findings suggest the potential to harness radiation-induced biology to ablate surviving quiescent cells and demonstrate Bcl-XL dependency as a potential vulnerability of surviving tumor cells after exposure to chemoradiation.

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Sensitivity of Human Tumor Cells to Retinoids or Combined Treatment with Retinoids and Ionizing Radiation is not Dependent on RAR-β2 Induction

Strahlentherapie und Onkologie ◽

10.1007/s00066-003-1030-3 ◽

2003 ◽

Vol 179 (6) ◽

pp. 401-409

Author(s):

Marcel A. Blaese ◽

Lan Santo-Hoeltje ◽

H. Peter Rodemann

Keyword(s):

Ionizing Radiation ◽

Tumor Cells ◽

Combined Treatment ◽

Human Tumor ◽

Human Tumor Cells

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Inhibition of Rac1 attenuates radiation-induced lung injury while suppresses lung tumor in mice

Cell Death Discovery ◽

10.1038/s41420-021-00791-8 ◽

2022 ◽

Vol 8 (1) ◽

Author(s):

Ni An ◽

Zhenjie Li ◽

Xiaodi Yan ◽

Hainan Zhao ◽

Yajie Yang ◽

...

Keyword(s):

Ionizing Radiation ◽

Lung Injury ◽

Mouse Model ◽

Tumor Cells ◽

Nuclear Translocation ◽

Lung Tumor ◽

Lung Epithelial Cells ◽

Normal Lung ◽

Limiting Factor ◽

Radiation Induced

AbstractThe lung is one of the most sensitive tissues to ionizing radiation, thus, radiation-induced lung injury (RILI) stays a key dose-limiting factor of thoracic radiotherapy. However, there is still little progress in the effective treatment of RILI. Ras-related C3 botulinum toxin substrate1, Rac1, is a small guanosine triphosphatases involved in oxidative stress and apoptosis. Thus, Rac1 may be an important molecule that mediates radiation damage, inhibition of which may produce a protective effect on RILI. By establishing a mouse model of radiation-induced lung injury and orthotopic lung tumor-bearing mouse model, we detected the role of Rac1 inhibition in the protection of RILI and suppression of lung tumor. The results showed that ionizing radiation induces the nuclear translocation of Rac1, the latter then promotes nuclear translocation of P53 and prolongs the residence time of p53 in the nucleus, thereby promoting the transcription of Trp53inp1 which mediates p53-dependent apoptosis. Inhibition of Rac1 significantly reduce the apoptosis of normal lung epithelial cells, thereby effectively alleviating RILI. On the other hand, inhibition of Rac1 could also significantly inhibit the growth of lung tumor, increase the radiation sensitivity of tumor cells. These differential effects of Rac1 inhibition were related to the mutation and overexpression of Rac1 in tumor cells.

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