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At least 19 recordsLinked to original sources
PubMed1977

Radiosensitization and radioprotection studies on Ehrlich ascites tumor. II. Experimental trial of lucanthone to enhance the radiosensitivity of the tumor.

Lucanthone (miracil D) is reported to be carcinostatic and a radiosensitizer. But in our study lucanthone alone (70 mg/kg body weight) had no lasting effect on the Ehrlich carcinoma in mice. Based on mitotic studies, 4-day old ascites tumor was not sensitized to X-rays when pretreated with lucanthone. Tumor growth, evaluated as the average weight of solid tumors or the number of tumor cells in ascites bearing mice, was not significantly different between the group treated with X-rays only and the one treated with lucanthone plus X-rays. Thus lucanthone seems to enhance the radiosensitivity of certain cell types but not of the tumor tested. The orobable mechanism of action of the drug leading in some cases to enhanced radiosensitivity is presented.

Animals↗
PubMed1975

Modest radiosensitization of solid tumours in C3H mice by the hypoxic cell radiosensitizer NDPP.

The x-ray dose required to cure half the mice bearing first generation transplanted mammary carcinomata 150 days after irradiation was determined. NDPP proved to be a relatively poor radiosensitizer in mice, for although a maximum enhancement ratio of 1-3 was obtained when x-rays produced from a 1-4 MeVp electron accelerator were given between 10 and 17 min after the administration of NDPP, this was at a drug concentration sufficient to cause marked kidney abnormalities in 5-10% of the mice.

Animals↗
PubMed2026

CRISPR Screen Identifies HDAC3 as a Novel Radiosensitizing Target in Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is an aggressive malignancy, with most patients presenting with prognostically poor extensive-stage disease. Limited progress in standard care stresses the urgent need for novel therapies. Radiotherapy offers some survival benefit for selected patients with SCLC but could be enhanced with radiosensitizers. In this study, we identify HDAC3 as a novel radiosensitizing target in SCLC using a CRISPR knockout screen and demonstrate its efficacy and mechanism. SBC5 cells were transduced with a custom EpiDrug single-guide RNA library and treated with ionizing radiation (IR) to identify radiosensitizing genes. HDAC3 emerged as a candidate and was validated through genetic knockdown and pharmacologic inhibition (RGFP966) in multiple SCLC cell lines. Both approaches enhanced radiosensitivity, as shown by cell viability (dose modification factor10 = 1.14-1.69) and clonogenic assays (dose modification factor10 = 1.16-1.41). We assessed changes in chromatin accessibility by assay for transposase-accessible chromatin using sequencing and IR-induced DNA damage and repair using γH2AX foci detection, double-strand break (DSB) repair assays, and immunoblotting of repair proteins. HDAC3-deficient cells exhibited increased chromatin accessibility, greater IR-induced DSBs, and impaired repair capacity, resulting in persistent DNA damage. This repair defect sensitized cells to PARP inhibitors, for which combining RGFP966 with olaparib or talazoparib produced additive to synergistic effects. In SCLC xenograft models, HDAC3 knockdown or RGFP966, combined with IR, achieved significant tumor growth inhibition. Collectively, we identified HDAC3 as a novel radiosensitizing target in SCLC. Its functional loss increased the generation and persistence of IR-induced DNA DSBs, effectively sensitizing SCLC cell lines and xenografts to IR, providing a potential radiosensitization strategy to treat SCLC.

Humans↗
PubMed1976

Cytological factors and their predictive role in comparative radiosensitivity: a general summary.

Various cytological factors, including interphase chromosome volume (ICV), nuclear volume (NV), cell volume, DNA content per nucleus and per chromosome, have been reviewed to determine their usefulness as indices to predict radiosensitivity. Fourteen topics are discussed. They are: a historical development of the concept of using karyotypic features to estimate radiosensitivity; interrelationships between cellular parameters; relationship of the karyotype to the duration of mitosis and meiosis; relationships between chronic and acute irradiation and ICV using several radiobiological end points for woody and herbaceous species; correlations between dose and cellular parameters ftween chromosome aberrations and cellular characteristics after chronic irradiation; polyploidy and plant radiosensitivity; radiation-induced petal mutations in plants and their relationship to cellular parameters; correlations between mean survival time facter irradiation and cellular parameters in amphibians and higher plants; correlations between radiobiological end points and cellular parameters after whole-body irradiation in amphibians. insects and mammals; correlations between radiosensitivity and cellular parameters in diverse single-cell organisms; correlations between radiobiological end points and cellular parameters in higher plants irradiated with neutrons and the value of cell parameters to estimate relative biological effectiveness (RBE); and energy absorption and trends in radiosensitivity among species and radiobiological end points. It is concluded that ICV is usually the most useful parameter for predicting radiosensitivity.

Amphibians↗
PubMed1978

Hypoxic cell radiosensitization by 8-methoxypsoralen.

8-Methoxypsoralen has been shown to act as a radiosensitizer of hypoxic bacteriophage and bacteria. Radiosensitization of bacteriophage requires irradiation in the presence of excess scavenger. Bacterial radiosensitization requires deficiencies in uvr and rec genes. For the drug to be effective it must be present during irradiation. Pulse radiolysis studies have shown that, like electron-affinic radiosensitizers, 8MOP can efficiently oxidize free radicals. Unlike oxygen and most electron-affinic radiosensitizers 8MOP does not act in a purely dose-modifying fashion, and can radiosensitize beyond the oxygen effect.

Coliphages↗
PubMed2026

Linking MRI radiomics to transcriptomics-based radiosensitivity in lower-grade glioma: A radiogenomic framework.

BACKGROUND: RSI is a transcriptomics-based biomarker associated with radiotherapy outcomes, but its clinical application is constrained by the requirement for tumor tissue and RNA sequencing. This study investigates whether MRI-derived radiomic features can reflect RSI-defined intrinsic radiosensitivity in lower-grade glioma.This addresses a critical gap arising from the limited availability of matched imaging and genomic data in routine clinical practice. METHODS: MRI-derived radiomic features were extracted from FLAIR images of lower-grade glioma patients obtained from TCIA and matched with transcriptomic data from TCGA. A total of 107 patients with both MRI and RNA sequencing data were included in the radiogenomic analysis. Radiomic features were ranked using a Borda-based ensemble feature selection strategy. Five supervised machine-learning classifiers were trained to predict RSI-based radiosensitivity classification, and model interpretability was assessed using SHAP within radiogenomic framework. RESULTS: Classification performance increased with feature number and stabilized at compact subset of 13 radiomic features. Logistic regression showed stable performance with an AUC of 0.82 (95 % CI: 0.71-0.93). SHAP analysis indicated that heterogeneity-related texture features were dominant contributors to model predictions, with many associated with the RR phenotype, while others were linked to the RS phenotype. CONCLUSION: An MRI-based radiomic signature enables non-invasive prediction of RSI-defined radiosensitivity in lower-grade glioma. Rather than offering an immediately deployable clinical tool, this study establishes a proof-of-concept radiogenomic framework demonstrating that intrinsic radiosensitivity, traditionally assessed through invasive molecular assays, can be approximated using quantitative imaging features. These findings highlight the potential of imaging-based radiosensitivity assessment and provide a foundation for future radiogenomic investigations.

Lower-grade glioma↗
PubMed2026

DDX21 Enhances Radiosensitivity in Head and Neck Squamous Cell Carcinoma by Suppressing MK2-Mediated DNA Damage Response.

Radioresistance remains a significant challenge in the radiotherapy (RT) of head and neck squamous cell carcinoma (HNSCC). However, the biological factors that govern sensitivity to this therapy are not well-understood. The DEAD-box family is known for its role in genome stability, and inextricably linked to the radiotherapy resistance of tumors. This study found the role of the RNA helicase DDX21 in regulating radiosensitivity through extensive data mining. High DDX21 expression predicted improved survival after postoperative radiotherapy. Overexpression of DDX21 increased radiosensitivity in vitro and in vivo, whereas depletion promoted radioresistance. In vitro, DDX21 enhanced radiation-induced DNA damage, genomic instability, and apoptosis by binding MK2 and suppressing MK2 phosphorylation independently of p38 activity. Meanwhile MK2 inhibition restored and further augmented radiosensitivity in DDX21-deficient cells and xenografts by increasing DNA damage and apoptosis. Overall, DDX21 regulates radiosensitivity in HNSCC by suppressing MK2 signaling and modulating the radiation-induced DNA damage response. Its expression may serve as a potential biomarker associated with radiosensitivity, and MK2 inhibition offers a promising approach to overcome radioresistance in tumors with low DDX21 expression.

DDX21↗
PubMed1978

Radiosensitivity of different B and T subpopulations of lymphocytes in the mouse spleen.

X-irradiation was used as a tool to investigate the radiosensitivity of different B and T precursor subpopulations as detected by three in vitro culture systems. The culture systems utilized in this study included antigen reactive cell assays (ARCA), polyclonal mitogen assays (PMA), and polyclonal effector cell assays (PECA). The order of radiosensitivity of these systems in both the B and T cell series was ARCA greater than PMA greater than PECA (D37 values for B cell responses: ARCA = 88.8 R, PMA = 125 R, PECA = 223 R; D37 values for T cell responses: ARCA = 160 R, PMA = 441 R and PECA = 1095 R). With all assay systems the B cell response was more radiosensitive than the T cell response. The extrapolation number (n) from the radiation survival curves was approximately 2.0 for T cell responses and approximately 1.0 for B cell responses. The value of 1.0 for B cell responses suggest that their extreme radiosensitivity may be due in part to a lack of repair mechanisms. These findings also suggest that the more primitive precursor cells are more apt to undergo cellular proliferation upon activation and that this event is more radiosensitive than is the final differentiation event of precursor cells into a progeny of functional end-stage cells.

Animals↗
PubMed1977

Corynebacterium parvum-induced radiosensitivity and cycling changes of hematopoietic spleen colony-forming units.

Ten days after total-body irradiation with 550 rads of b0Co, spleen colonies were observed in adult C57BL mice. A change in radiosensitivity induced by Corynebacterium parvum, as measured by increased numbers of colony-forming units that survived the 550 rads, began shortly after C. parvum stimulation and extended for at least 7 days before irradiation. C. parvum given 4-24 hours before, followed by high specific activity [3H]thymidine (HSATT) 1 hour before total-body irradiation greatly reduced survival of the stem cells that formed spleen colonies (CFUs) and CFUs radiosensitivity to control levels. The HSATT sensitivity by "suicide" assay in vivo and the time-response change in radiosensitivity corresponded with the decrease in radiosensitivity, which showed that CFUs were stimulated by C. parvum administration and entered the S-phase shortly after stimulation. The data indicated a resting population close to the S-phase. After stimulation, this population entered S-phase. Syngeneic mouse lymphoma cells injected iv 24 hours earlier did not elicit any effect as a stimulus to CFUs radiosensitivity change.

Animals↗
PubMed1978

Profound radiosensitivity in "leukemic" T-cell lines and T-cell-type acute lymphoblastic leukemia demonstrated by sodium [51Cr]chromate labeling.

Radiation sensitivity was determined by measuring spontaneous release from 51Cr-labeled cells in various lymphoid cell populations. Among six leukemia T-cell lines originating from acute lymphoblastic leukemia, four such lines were found to be highly radiosensitive. In contrast, two of the leukemic T-cell lines and four normal control B-cell lines were not radiosensitive. Thymocytes from six patients and leukemia T-cell blasts from three patients with T-cell leukemia were likewise found to be highly radiosensitive, whereas leukemic blasts from six patients with null-cell (non-T, non-B-cell) acute lymphoblastic leukemia were not radiosensitive. Normal peripheral blood lymphocytes and mitogen-induced normal lymphoblasts were found not to be radiosensitive. The results indicate that measurement of the radiation sensitivity of acute leukemic blasts may have a therapeutic significance in coping with the heterogeneous nature of individual leukemia cases.

Animals↗
PubMed1979

Pharmacokinetic considerations in testing hypoxic cell radiosensitizers in mouse tumours.

Bilateral kidney ligation of mice immediately before injection of misonidazole (MIS) prolongs the plasma half-life of this radiosensitizer from about 2 h (in normal mice) to 10-11 h, similar to that in man. Kidney ligation does not, however, change the relative proportions of MIS and its O-demethylated metabolite, Ro-05-9963, for the first 12 h after MIS injection. Kidney ligation was used with the two radiosensitizers, MIS and Ro-05-9963, to investigate the influence of plasma half-life both on peak plasma levels and on the tumour/plasma ratio of sensitizer concentration in the EMT6 mouse tumour. Although the acute LD50 of Ro-05-9963 in normal mice was twice that of MIS, this apparent advantage was offset by peak tumour levels 50% or less of those achieved by equimolar injected doses of MIS. However, by comparing the plasma and tumour levels in mice in which the drug half-lives were prolonged by bilateral kidney ligation, it was concluded that the lower plasma and tumour levels of Ro-05-9963 were a result of its shorter plasma half-life, rather than of an intrinsic barrier to tumour penetration. Because of this rapid clearance, the radiosensitization produced by Ro-05-9963 was less than that produced by equimolar injected doses of MIS. As this difference did not occur in kidney-ligated mice, and hence would not be expected to occur in man, the comparison of MIS and Ro-05-9963 in mice produces an artificially low radiosensitization for Ro-05-9963 and possibly also for other compounds with short plasma half-lives. Although the short plasma half-life of Ro-05-9963 appeared to be responsible for its low peak plasma concentration, it did not produce a low tumour/plasma ratio. Within the limits of plasma nitroimidazole half-lives investigated (0.5-10 h) the tumour/plasma ratio was insensitive to plasma half-life, being 50-70% for both MIS and Ro-05-9963 in both normal and kidney-ligated mice. It is concluded that the common assumption that tumour/plasma ratios of MIS in the mouse are less than those in man is unjustified.

Animals↗
PubMed1977

Free-radical formation in gamma-irradiated oriented DNA containing electron-affinic radiosensitizers.

Electron paramagnetic resonance (e.p.r.) was used to study the free radicals induced by gamma-irradiation at 77 K in oriented DNA with incorporated electronaffinic radiosensitizing compounds (4-nitroacetophenone, metronidazole, and Ro-07-0582). The observed e.p.r. spectra were compared with those obtained from pure oriented DNA, which had previously been analysed in detail and found to consist mainly of two components, arising from anion redicals on thymine, and cation radicals on guanine. The major spectral changes caused by the radiosensitizers could be explained as a considerable increase in the formation of cationic free radicals on guanine. There were also indications of the formation of anion radicals on the radiosensitizer molecules. No hydrogen-addition free radicals on thymine were observed when the radiosensitized samples were annealed, in contrast to the pure DNA samples.

Acetophenones↗
PubMed1979

Photosensitizers and radiosensitizers in dermatology and oncology.

Two therapeutic modalities are currently of great interest, namely photo- and radiosensitization. Whereas photosensitizers only function in combination with ultraviolet (UV) light, radiosensitizers act only in combination with ionizing radiation. Because of the small UV penetration, up to a maximum of 0,5 mm, photosensitization can take place only at the surface of the body, ie. the skin. Photosensitizers are applied in dermatology in order to optimize and improve the UV therapy of certain diseases (mainly psoriasis, mycosis fungoides and vitiligo). Radiosensitizers lead to an increase in sensitivity of the hypoxic and therefore radioresistant parts of tumours against X- and gamma-radiation. With sufficient concentration within the tumour, they can act where the radiation can reach, even in the deeper parts of the body. They represent a modern and useful aid to radiation oncology. Because of neurotoxic effects, however, their practical use is limited. A short review of the history, mechanisms of action, application and side-effects of these photo- and radiosensitizers is presented.

Brain Neoplasms↗